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Categories:

  • Vaccine Contamination Studies

  • Vaccine Associated Food Allergies

  • Vaccine Associated Autism

  • Vaccine Associated Antibody Dependent Enhancement

  • Infant Mortality Rates and Vaccines

  • Vaccinated Verses Non – or Under-vaccinated Children

  • Influenza Vaccine Description and Reactions

  • Human Papilloma Virus Vaccine Description and Reactions

  • Diphtheria Vaccine Description and Reactions

  • Pertussis Vaccine Description and Reactions

  • Tetanus Vaccine Description and Reactions

  • Hepatitis B Vaccine Description and Reactions

  • Measles, Mumps, Rubella Vaccine Description and Reactions

  • Polio Vaccine Description and Reactions

  • Polio Vaccine Live Vs. Killed Virus History

  • Polio Vaccine History and Simian Virus 40 (SV40)

  • Shingles Vaccine Description and Reactions

  • Varicella (Chickenpox) Vaccines Description and Reactions

Vaccine Contamination Studies

Arumugham, Vinu, and Maxim V. Trushin. "Cancer immunology, bioinformatics and chemokine evidence link vaccines contaminated with animal proteins to autoimmune disease: a detailed look at Crohn's disease and Vitiligo." Journal of Pharmaceutical Sciences and Research 10, no. 8 (2018): 2106-2110.

Conclusion

Cancer research has demonstrated that immunization with homologous xenogeneic proteins (such as vaccines contaminated with animal proteins that resemble human proteins) results in autoimmunity. Bioinformatics analysis demonstrates that animal proteins have occasional amino acid differences compared to equivalent human proteins. For this purpose, we used Uniprot and BLASTP. We found homology to human GP2 (Bos taurus 77%, Sus scrofa 76%, Cavia porcellus 72% Gallus gallus 43%), homology to human tyrosinase (Bos taurus 87%, Sus scrofa 90%, Cavia porcellus 85%, Gallus gallus 73%), homology to human GP100 (Bos taurus 77%, Sus scrofa 81%, Cavia porcellus 77%, Gallus gallus 42%) and highlight the occasional amino acid differences. Mutated human protein epitopes can be identical to animal protein derived epitopes. Low affinity self-reactive T cells suited for detection of mutated human epitopes will be activated by animal derived epitopes. CD8+ T cells involved in numerous autoimmune disorders express the CCR4 skin homing receptor. This is evidence that the site of priming was the skin. This is consistent with subcutaneous or intramuscular injection of animal protein contaminated vaccines. The above findings add to the growing evidence of vaccines inducing autoimmune diseases. Autoantibody and autoreactive T cell levels can vary from person to person. Not everyone will develop overt disease. For every case of diagnosed autoimmune disease, there are numerous subclinical cases. These subclinical diseases could shave decades off your life. So “rare” diagnosed vaccine adverse events are the tip of the iceberg.

 

Gatti, Antonietta M., and Stefano Montanari. "New quality-control investigations on vaccines: micro-and nanocontamination." Int J Vaccines Vaccin 4, no. 1 (2016): 00072.

 

Summary: Scientists found contaminants in all vaccines that are not listed on the label of the vaccines. "The analyses carried out show that in all samples checked vaccines contain non biocompatible and bio-persistent foreign bodies which are not declared by the Producers, against which the body reacts in any case. This new investigation represents a new quality control that can be adopted to assess the safety of a vaccine. Our hypothesis is that this contamination is unintentional, since it is probably due to polluted components or procedures of industrial processes (e.g. filtrations) used to produce vaccines, not investigated and not detected by the Producers. If our hypothesis is actually the case, a close inspection of the working places and the full knowledge of the whole procedure of vaccine preparation would probably allow to eliminate the problem."

Abstract

Vaccines are being under investigation for the possible side effects they can cause. In order to supply new information, an electron-microscopy investigation method was applied to the study of vaccines, aimed at verifying the presence of solid contaminants by means of an Environmental Scanning Electron Microscope equipped with an X-ray microprobe. The results of this new investigation show the presence of micro- and nanosized particulate matter composed of inorganic elements in vaccines’ samples which is not declared among the components and whose unduly presence is, for the time being, inexplicable. A considerable part of those particulate contaminants have already been verified in other matrices and reported in literature as non-biodegradable and non-biocompatible. The evidence collected is suggestive of some hypotheses correlated to diseases that are mentioned and briefly discussed.

Vaccine Associated Food Allergies

 

Arumugham, Vinu. "Evidence that Food Proteins in Vaccines Cause the Development of Food Allergies and Its Implications for Vaccine Policy." Journal of Developing Drugs (2015).

Abstract 

Nobel Laureate Charles Richet demonstrated over a hundred years ago that injecting a protein into animals or humans causes immune system sensitization to that protein. Subsequent exposure to the protein can result in allergic reactions or anaphylaxis. This fact has since been demonstrated over and over again in humans and animal models. The Institute of Medicine (IOM) confirmed that food proteins in vaccines cause food allergy, in its 2011 report on vaccine adverse events. The IOM’s confirmation is the latest and most authoritative since Dr. Richet’s discovery. Many vaccines and injections contain food proteins. Many studies since 1940 have demonstrated that food proteins in vaccines cause sensitization in humans. Allergens in vaccines are not fully disclosed. No safe dosage level for injected allergens has been established. As a result, allergen quantities in vaccines and injections are not regulated. Allergen quantities in vaccine excipients are also not regulated. It has been demonstrated that a smaller quantity of allergen is needed to cause sensitization than elicitation. It is well recognized that many currently approved vaccines have enough allergen to cause anaphylaxis. Therefore, they contain more than enough allergen to cause sensitization. Children today have fewer childhood infectious diseases. They have less exposure to helminths. C-section birth rates have increased in the last few decades by 50%. C-section births are known to result in sub-optimal gut microbiome in the newborn. All the above result in an immune imbalance biased towards atopy. Vaccine schedules today include 30-40 shots. Up to five shots may be simultaneously administered in one sitting. Vaccines contain adjuvants such as pertussis toxins and aluminum compounds that also bias towards allergy. Adjuvants also increase the immunogenicity of injected food proteins. This combination of atopic children and food protein injection along with adjuvants, contributes to millions developing life-threatening food allergies. Given the scale and severity of the food allergy epidemic, urgent action is needed to change vaccine policy concerning vaccine specifications, manufacture, vaccine package insert documentation requirements, the Vaccine Adverse Event Reporting System (VAERS) and the National Vaccine Injury Compensation program. Many researchers have called for the removal of food proteins from vaccines and re-evaluation of adjuvants such as aluminum compounds. In the interim, food allergy warnings can be included in vaccine package inserts. Simultaneous administration of multiple vaccines can be stopped to avoid the combined negative effects of multiple food proteins and adjuvants.


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Infant Mortality Rates and Vaccines

Miller, Neil Z., and Gary S. Goldman. "Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity?." Human & Experimental Toxicology 30, no. 9 (2011): 1420-1428.

 

Conclusion

The US childhood immunization schedule requires 26 vaccine doses for infants aged less than 1 year, the most in the world, yet 33 nations have better IMRs. Using linear regression, the immunization schedules of these 34 nations were examined and a correlation coefficient of 0.70 (p < 0.0001) was found between IMRs and the number of vaccine doses routinely given to infants. When nations were grouped into five different vaccine dose ranges (12–14, 15–17, 18–20, 21–23, and 24–26), 98.3% of the total variance in IMR was explained by the unweighted linear regression model. These findings demonstrate a counter-intuitive relationship: nations that require more vaccine doses tend to have higher infant mortality rates.

Efforts to reduce the relatively high US IMR have been elusive. Finding ways to lower preterm birth rates should be a high priority. However, preventing premature births is just a partial solution to reduce infant deaths. A closer inspection of correlations between vaccine doses, biochemical or synergistic toxicity, and IMRs, is essential. All nations—rich and poor, advanced, and developing—have an obligation to determine whether their immunization schedules are achieving their desired goals.

 

Vaccinated Verses Non – or Under-vaccinated Children

Glanz, Jason M., Sophia R. Newcomer, Komal J. Narwaney, Simon J. Hambidge, Matthew F. Daley, Nicole M. Wagner, David L. McClure et al. "A population-based cohort study of undervaccination in 8 managed care organizations across the United States." JAMA pediatrics 167, no. 3 (2013): 274-281.

 

Results: 

Of 323 247 children born between 2004 and 2008, 48.7% were undervaccinated for at least 1 day before age 24 months. The prevalence of undervaccination and specific patterns of undervaccination increased over time (P.001). In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR],0.89; 95% CI, 0.89-0.90). In a second matched cohort analysis, children who were undervaccinated because of parental choice had lower rates of outpatient visits (IRR,0.94; 95% CI, 0.93-0.95) and emergency department encounters (IRR,0.91; 95% CI, 0.88-0.94) than age-appropriately vaccinated children.

 

Influenza Vaccine Description and Reactions

There are several different influenza vaccines licensed by the U.S. Food and Drug Administration (FDA) and distributed by manufacturers for use in the U.S. that are recommended by the US Centers for Disease Control (CDC) for different age groups.  Most seasonal influenza vaccines in the U.S. contain either two type A influenza viruses and one type B influenza virus (Trivalent) or two type A influenza viruses and two type B influenza viruses (Quadrivalent) that are selected every year by the World Health Organization (WHO) and U.S. Centers for Disease Control (CDC) for inclusion in influenza vaccines given during the current flu season. 

 

Most of the influenza vaccines in use in the U.S. are injectable, inactivated vaccines that are made using chicken embryos, insect cells, or dog kidney cells. Depending upon the vaccine manufacturer, some influenza vaccines contain an oil in water squalene adjuvant that hyper-stimulates the immune system to produce a stronger antibody response.  Injectable influenza vaccines packaged in multi-dose vials contain the mercury preservative thimerosal, and inactivated influenza vaccines packaged in single dose vials are either thimerosal-free or contain trace amounts of the mercury preservative, while the live attenuated nasal vaccine contains no thimerosal.  

 

The CDC recommends that all Americans six months of age or older get a flu shot every year and that babies between six and eight months old receive two doses of influenza vaccine one month apart in the first year of life.  The CDC reports that between 2004/2005 and 2018/2019, overall influenza vaccine effectiveness ranged from 10 percent (2004/2005) to 60 percent (2010/2011) and the vaccine was less than 50 percent effective in 11 out of 15 flu seasons.

 

Using the MedAlerts search engine, as of July 31, 2020, there have been more than 176,294 reports of influenza vaccine reactions, hospitalizations, injuries and deaths following influenza vaccinations made to the federal Vaccine Adverse Events Reporting System (VAERS), including 1,748 related deaths, 14,062 hospitalizations, and 3,558 related disabilities. Moderate reactions reported include fever, local reactions (pain, redness, swelling at the site of the injection), headache, fatigue, sore throat, nasal congestion, cough, joint and muscle pain, and nausea. Serious vaccine complications include brain inflammation and neurological damage, convulsions, Bell’s palsy, limb paralysis, neuropathy, shock, wheezing/asthma and other breathing problems, and death. Influenza vaccinations can cause Guillain Barre Syndrome (GBS), a painful and disabling immune and neurological disorder of the peripheral nervous system that can cause temporary or permanent paralysis and death.

 

In 2013, the Federal Advisory Commission on Childhood Vaccines (ACCV) voted to add GBS to the Vaccine Injury Table (VIT) within the federal Vaccine Injury Compensation Program (VICP) and it was officially added in 2017. As of September 1, 2020, there have been 6,441 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following influenza vaccination, including 188 deaths and 6,256 serious injuries.

 

Source: NVIC.ORG

Articles Influenza Vaccine Reactions

 

Duffy, Jonathan, Eric Weintraub, Simon J. Hambidge, Lisa A. Jackson, Elyse O. Kharbanda, Nicola P. Klein, Grace M. Lee et al. "Febrile seizure risk after vaccination in children 6 to 23 months." Pediatrics 138, no. 1 (2016).

Abstract

BACKGROUND AND OBJECTIVE:

An increased risk of febrile seizure (FS) was identified with concomitant administration of trivalent inactivated influenza vaccine (IIV3) and pneumococcal conjugate vaccine (PCV) 13-valent during the 2010–2011 influenza season. Our objective was to determine whether concomitant administration of IIV3 with other vaccines affects the FS risk.

METHODS:

We examined the risk of FS 0 to 1-day postvaccination for all routinely recommended vaccines among children aged 6 through 23 months during a period encompassing 5 influenza seasons (2006–2007 through 2010–2011). We used a population-based self-controlled risk interval analysis with a control interval of 14 to 20 days postvaccination. We used multivariable regression to control for receipt of concomitant vaccines and test for interaction between vaccines.

RESULTS:

Only PCV 7-valent had an independent FS risk (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.00 to 3.91). IIV3 had no independent risk (IRR, 0.46; 95% CI, 0.21 to 1.02), but risk was increased when IIV3 was given with either PCV (IRR, 3.50; 95% CI, 1.13 to 10.85) or a diphtheria-tetanus-acellular-pertussis (DTaP)-containing vaccine (IRR, 3.50; 95% CI, 1.52 to 8.07). The maximum estimated absolute excess risk due to concomitant administration of IIV3, PCV, and DTaP-containing vaccines compared with administration on separate days was 30 FS per 100 000 persons vaccinated.

CONCLUSIONS:

The administration of IIV3 on the same day as either PCV or a DTaP-containing vaccine was associated with a greater risk of FS than when IIV3 was given on a separate day. 

 

Evans, David, Simon Cauchemez, and Frederick G. Hayden. “Prepandemic” immunization for novel influenza viruses, “swine flu” vaccine, Guillain-Barre syndrome, and the detection of rare severe adverse events." Journal of Infectious Diseases 200, no. 3 (2009): 321-328.

 

Greene, Sharon K., Melisa Rett, Eric S. Weintraub, Lingling Li, Ruihua Yin, Anthony A. Amato, Doreen T. Ho et al. "Risk of confirmed Guillain-Barré syndrome following receipt of monovalent inactivated influenza A (H1N1) and seasonal influenza vaccines in the Vaccine Safety Datalink Project, 2009–2010." American journal of epidemiology 175, no. 11 (2012): 1100-1109.

 

Haber, Penina, Frank DeStefano, Fredrick J. Angulo, John Iskander, Sean V. Shadomy, Eric Weintraub, and Robert T. Chen. "Guillain-Barré syndrome following influenza vaccination." Jama 292, no. 20 (2004): 2478-2481.

 

Lehmann, Helmar C., Hans-Peter Hartung, Bernd C. Kieseier, and Richard AC Hughes. "Guillain-Barré syndrome after exposure to influenza virus." The Lancet infectious diseases 10, no. 9 (2010): 643-651.

 

Schonberger, Lawrence B., Dennis J. Bregman, John Z. Sullivan-Bolyai, Richard A. Keenlyside, Donald W. Ziegler, Henry F. Retailliau, Donald L. Eddins, and John A. Bryan. "Guillain-Barré syndrome following vaccination in the national influenza immunization program, United States, 1976–1977." American journal of epidemiology 110, no. 2 (1979): 105-123.

 

Vellozzi, Claudia, Karen R. Broder, Penina Haber, Alice Guh, Michael Nguyen, Maria Cano, Paige Lewis et al. "Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009–January 31, 2010." Vaccine 28, no. 45 (2010): 7248-7255.

 

Human Papilloma Virus Vaccine Description and Reactions

There are three FDA licensed HPV vaccines, however only one, Gardasil 9, approved in 2014 and manufactured by Merck, is currently available in the United States. Initially, HPV vaccines were given as a series of three shots over 6 months to protect against HPV infection and the health problems that ongoing HPV infection can cause. In 2016 the CDC recommended a two-dose series with second dose administration between 6 to 12 months from the first dose. Below is information on the HPV vaccines licensed in the U.S.

  • Gardasil 9: FDA approved Gardasil 9 for use in 2014. The safety of Gardasil 9 was studied in clinical trials with more than 15,000 participants before it was licensed and continues to be monitored. According to Merck’s product insert, Gardasil 9 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

  • Gardasil: FDA approved Gardasil for use in 2006. The safety of Gardasil was studied in clinical trials with more than 29,000 participants before it was licensed. According to Merck’s product insert, Gardasil protects against HPV types 6, 11, 16, and 18.

  • Cervarix: FDA approved Cervarix for use in 2009. The safety of Cervarix was studied in clinical trials with more than 30,000 participants before it was licensed. According to GlaxoSmithKine’s product insert, Cervarix protects women and girls against HPV types 16 and 18.

 

Source: NVIC.ORG

Articles Human Papilloma Virus Vaccine Reactions

Colafrancesco, Serena, Carlo Perricone, Lucija Tomljenovic, and Yehuda Shoenfeld. "Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants." American Journal of Reproductive Immunology 70, no. 4 (2013): 309-316.

 

Abstract

Problem Post-vaccination autoimmune phenomena are a major facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and different vaccines, including HPV, have been identified as possible causes. 

Method of study:

The medical history of three young women who presented with secondary amenorrhea following HPV vaccination was collected. Data regarding type of vaccine, number of vaccinations, personal, clinical and serological features, as well as response to treatments were analyzed. Results All three patients developed secondary amenorrhea following HPV vaccinations, which did not resolve upon treatment with hormone replacement therapies. In all three cases sexual development was normal and genetic screen revealed no pertinent abnormalities (i.e., Turner’s syndrome, Fragile X test were all negative). Serological evaluations showed low levels of estradiol and increased FSH and LH and in two cases, specific autoantibodies were detected (antiovarian and anti-thyroid), suggesting that the HPV vaccine triggered an autoimmune response. Pelvic ultrasound did not reveal any abnormalities in any of the three cases. All three patients experienced a range of common non-specific post-vaccine symptoms including nausea, headache, sleep disturbances, arthralgia, and a range of cognitive and psychiatric disturbances. According to these clinical features, a diagnosis of primary ovarian failure (POF) was determined which also fulfilled the required criteria for the ASIA syndrome. Conclusion We documented here the evidence of the potential of the HPV vaccine to trigger a life-disabling autoimmune condition. The increasing number of similar reports of post HPV vaccine-linked autoimmunity and the uncertainty of long-term clinical benefits of HPV vaccination are a matter of public health that warrants further rigorous inquiry.

Gruber, Noah, and Yehuda Shoenfeld. "A link between human papilloma virus vaccination and primary ovarian insufficiency: current analysis." Current Opinion in Obstetrics and Gynecology 27, no. 4 (2015): 265-270.

 

Recent findings 

Vaccine Associated Autism

 

Arumugham, Vinu. "Epidemiological studies that ignore mechanism of disease causation are flawed and mechanistic evidence demonstrates that vaccines cause autism." proteins 13 (2017): 16.

 

Conclusion

Despite their success, one of the great ironies of vaccinology is that the vast majority of vaccines have been developed empirically, with little or no understanding of the immunological mechanisms by which they induce protective immunity. However, the failure to develop vaccines against global pandemics such as infection with human immunodeficiency virus despite decades of effort has underscored the need to understand the immunological mechanisms by which vaccines confer protective immunity.” Since vaccinologists are themselves ignorant of vaccine mechanisms, how can we expect epidemiologists to understand the mechanisms? So most epidemiological studies ignore mechanism of adverse event causation. If you ignore mechanism, you cannot design the study with appropriate controls. So, the results of such epidemiological studies must be discarded.

 

Singh VK, Sheren XL, Yang VC. 1998. "Serological association of measles virus and human herpesvirus-6 with brain autoantibiodies in autism." Clinical Immunology 

 

Abstract

Considering an autoimmunity and autism connection, brain autoantibodies to myelin basic protein (anti-MBP) and neuron–axon filament protein (antiNAFP) have been found in autistic children. In this current study, we examined associations between virus serology and autoantibody by simultaneous analysis of measles virus antibody (measles-IgG), human herpesvirus-6 antibody (HHV-6-IgG), anti-MBP, and anti-NAFP. We found that measles-IgG and HHV-6-IgG titers were moderately higher in autistic children, but they did not significantly differ from normal controls. Moreover, we found that a vast majority of virus serology-positive autistic sera was also positive for brain autoantibody: (i) 90% of measles-IgG-positive autistic sera was also positive for anti-MBP; (ii) 73% of measles-IgG-positive autistic sera was also positive for anti-NAFP; (iii) 84% of HHV-6-IgG-positive autistic sera was also positive for anti-MBP; and (iv) 72% of HHV-6- IgG-positive autistic sera was also positive for antiNAFP. This study is the first to report an association between virus serology and brain autoantibody in autism; it supports the hypothesis that a virus-induced autoimmune response may play a causal role in autism.

Singh, Vijendra K., Sheren X. Lin, Elizabeth Newell, and Courtney Nelson. "Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism." Journal of biomedical science 9, no. 4 (2002): 359-364.

 

Abstract 

Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measles mumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73–75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus, the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism.

 

Singh, Vijendra K., and Ryan L. Jensen. "Elevated levels of measles antibodies in children with autism." Pediatric neurology 28, no. 4 (2003): 292-294.

Abstract

Virus-induced autoimmunity may play a causal role in autism. To examine the etiological link of viruses in this brain disorder, we conducted a serological study of measles virus, mumps virus, and rubella virus. Viral antibodies were measured by enzyme-linked immunosorbent assay in the serum of autistic children, normal children, and siblings of autistic children. The level of measles antibody, but not mumps or rubella antibodies, was significantly higher in autistic children as compared to normal children (p  .003) or siblings of autistic children (p < .0001). Furthermore, immunoblotting of measles vaccine virus showed that the antibody was directed against a protein of approximately 74 kd molecular weight. The antibody to this antigen was found in 83% of autistic children but not in normal children or siblings of autistic children. Thus, autistic children have a hyper-immune response to measles virus, which in the absence of a wild-type measles infection might be a sign of an abnormal immune reaction to the vaccine strain or virus reactivation

Vaccine Associated Antibody Dependent Enhancement

 

Vaccine autoimmunity reactions occur from several causes. One of the most documented causes antibody dependent enhancement (ADE) also known as pathogenic priming or disease enhancement. Disease enhancement may occur after vaccination or when an infection a person can experience more serious, enhanced disease when later being exposed to the pathogen against which that the vaccine was intended to protect. 

Thus, ADE is a biochemical mechanism in which virus-specific antibodies (usually from a vaccine) promote the entry and/or the replication of another virus into white cells such as monocytes/macrophages and granulocytic cells. This then modulates an overly strong immune response (abnormally enhances it) and induces chronic inflammation, lymphopenia, and/or a ‘cytokine storm’, one or more of which have been reported to cause severe illness and even death. Essentially, ADE is a disease dissemination cycle causing individuals with secondary infection to be more immunologically upregulated than during their first infection (or prior vaccination) by a different strain.

 

In antibody-mediated viral neutralization, neutralizing antibodies binding to the receptor-binding domain of the viral spike protein, as well as other domains, prevent the virus from docking onto its entry receptor. In antibody-dependent enhancement, low quality, low quantity, non-neutralizing antibodies bind to virus particles through the antigen-binding fragment or Fab domains. Fc receptors (FcRs) expressed on monocytes or macrophages bind to Fc domains of antibodies and facilitate viral entry and infection. (An Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system.) Upon engagement by the Fc domains on antibodies, activating FcRs with ITAMs initiate signaling to upregulate pro-inflammatory cytokines and downregulate anti-inflammatory cytokines. This causes what is commonly described as a cytokine storm. Immune complexes and viral RNA in the endosomes can signal through Toll-like receptor 3 (TLR3), TLR7, and/or TLR8 to activate host cells, resulting in immunopathology.

 

Articles Vaccine Associated Antibody Dependent Enhancement

Beck, Zoltán, Zoltán Prohászka, and George Füst. "Traitors of the immune system—enhancing antibodies in HIV infection: their possible implication in HIV vaccine development." Vaccine 26, no. 24 (2008): 3078-3085.

Abstract

Considering recent HIV vaccine failures, the authors believe that it would be most important to find new targets for vaccine-induced immunity, and to analyze the data from previous trials, using an innovative approach. In their review article, the authors briefly summarize the significance of the antibody-dependent enhancement of infection in different viral diseases and discuss role of these types of antibodies as the obstacles for vaccine development. Findings which indicate that complement-mediated antibody-dependent enhancement (C-ADE) is present also in HIV-infected patients, are summarized. Previous results of the authors, suggesting that C-ADE plays a very important role in the progression of HIV infection are described. Data reflecting that enhancing antibodies may develop even in vaccinated animals and human volunteers and may be responsible for the paradoxical results obtained in some subgroups of vaccinees are discussed. Finally, based on their hypothesis, the authors offer some suggestions for the future development of vaccines.

 

Bolles, Meagan, Damon Deming, Kristin Long, Sudhakar Agnihothram, Alan Whitmore, Martin Ferris, William Funkhouser et al. "A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge." Journal of virology 85, no. 23 (2011): 12201-12215.

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted doubleinactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.

 

Czub, Markus, Hana Weingartl, Stefanie Czub, Runtao He, and Jingxin Cao. "Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets." Vaccine 23, no. 17-18 (2005): 2273-2279.

Abstract

Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) remains a threat to cause epidemics as evidenced by recent sporadic cases in China. In this communication, we evaluated the efficacy and safety of two SARS vaccine candidates based on the recombinant modified vaccinia Ankara (MVA) expressing SARS-CoV spike or nucleocapsid proteins in ferrets. No clinical signs were observed in all the ferrets challenged with SARS-CoV. On the other hand, vaccination did not prevent SARS-CoV infection in ferrets. In contrast, immunized ferrets (particularly those immunized with rMVA-spike) exhibited significantly stronger inflammatory responses and focal necrosis in liver tissue after SARS-CoV challenge than control animals. Thus, our data suggest that enhanced hepatitis is linked to vaccination with rMVA expressing SARS-CoV antigens.

 

Gauger PC, Vincent AL, Loving CL, Lager KM, Janke BH, Kehrli ME Jr., and Roth JA: "Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (delta-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus." Vaccine 2011;29:2712–2719.

Abstract

Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies.

 

Kam, Yiu Wing, François Kien, Anjeanette Roberts, Yan Chung Cheung, Elaine W. Lamirande, Leatrice Vogel, Shui Ling Chu et al. "Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcγRII-dependent entry into B cells in vitro." Vaccine 25, no. 4 (2007): 729-740. 

 

Abstract

Vaccine-induced antibodies can prevent or, in the case of feline infectious peritonitis virus, aggravate infections by coronaviruses. We investigated whether a recombinant native full-length S-protein trimer (triSpike) of severe acute respiratory syndrome coronavirus (SARS-CoV) was able to elicit a neutralizing and protective immune response in animals and analyzed the capacity of anti-S antibodies to mediate antibody-dependent enhancement (ADE) of virus entry in vitro and enhancement of replication in vivo. SARS-CoV-specific serum and mucosal immunoglobulins were readily detected in immunized animals. Serum IgG blocked binding of the S-protein to the ACE2 receptor and neutralized SARS-CoV infection in vitro. Entry into human B cell lines occurred in a FcγRII-dependent and ACE2-independent fashion indicating that ADE of virus entry is a novel cell entry mechanism of SARS-CoV. Vaccinated animals showed no signs of enhanced lung pathology or hepatitis and viral load was undetectable or greatly reduced in lungs following challenge with SARS-CoV. Altogether our results indicate that a recombinant trimeric S protein was able to elicit an efficacious protective immune response in vivo and warrant concern in the safety evaluation of a human vaccine against SARS-CoV.

Kim, Hyun Wha, JOSE G. CANCHOLA, CARL D. BRANDT, GLORIA PYLES, ROBERT M. CHANOCK, KEITH JENSEN, and ROBERT H. PARROTT. "Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine." American journal of epidemiology 89, no. 4 (1969): 422-434. 

 

Abstract

In response to three injections of alum precipitated, 100X concentrated, formalin inactivated RS vaccine (tot 100), 43 % of infant vaccinees displayed a 4-fold or greater rise in serum neutralizing antibody and 91 % displayed a 4-fold or greater rise in serum CF antibody. When RS virus became prevalent in the community, the rate of RS virus infection in infants who received this vaccine was not remarkably different from that in control infants who received parainfluenza vaccines. However, 80 % of RS vaccinees required hospitalization at the time of RS infection whereas only 5 % of such infections among parainfluenza vaccinees resulted in admission to the hospital. Illnesses among the RS vaccinees who underwent natural infection included pneumonia, bronchiolitis, and bronchiolitis with pneumonia in a majority and rhinitis, pharyngitis, and bronchitis in a few. It seems clear that infants who received this vaccine were not protected against natural infection and, when they became naturally infected their illness was more severe than that seen in cohorts who received a similar parainfluenza type 1 vaccine. These findings indicate that vaccine-induced RS virus serum antibody alone does not protect against illness and suggest that serum antibody without local respiratory antibody may play a part in the production of disease. We have also observed that the highest incidence of serious RS virus illness occurring naturally is under six months of age when maternally derived serum antibody is present. These findings together suggest that RS virus illness in infants is an immunologic phenomenon wherein the virus and serum antibody interact to produce severe illness.

 

Tirado, S. M. C., & Yoon, K. J. (2003). "Antibody-dependent enhancement of virus infection and disease. Viral immunology," 16(1), 69-86.

 

Abstract

In general, virus-specific antibodies are considered antiviral and play an important role in the control of virus infections in a number of ways. However, in some instances, the presence of specific antibodies can be beneficial to the virus. This activity is known as antibody-dependent enhancement (ADE) of virus infection. The ADE of virus infection is a phenomenon in which virus-specific antibodies enhance the entry of virus, and in some cases the replication of virus, into monocytes/macrophages and granulocytic cells through interaction with Fc and/or complement receptors. This phenomenon has been reported in vitro and in vivo for viruses representing numerous families and genera of public health and veterinary importance. These viruses share some common features such as preferential replication in macrophages, ability to establish persistence, and antigenic diversity. For some viruses, ADE of infection has become a great concern to disease control by vaccination. Consequently, numerous approaches have been made to the development of vaccines with minimum or no risk for ADE. Identification of viral epitopes associated with ADE or neutralization is important for this purpose. In addition, clear understanding of the cellular events after virus entry through ADE has become crucial for developing efficient intervention. However, the mechanisms of ADE still remain to be better understood.

 

Takada, Ayato, and Yoshihiro Kawaoka. "Antibody‐dependent enhancement of viral infection: molecular mechanisms and in vivo implications." Reviews in medical virology 13, no. 6 (2003): 387-398.

Abstract

Besides the common receptor/coreceptor‐dependent mechanism of cellular attachment, some viruses rely on antiviral antibodies for their efficient entry into target cells. This mechanism, known as antibody‐dependent enhancement (ADE) of viral infection, depends on the cross‐linking of complexes of virus–antibody or virus–activated complement components through interaction with cellular molecules such as Fc receptors or complement receptors, leading to enhanced infection of susceptible cells. Recent studies have suggested that additional mechanisms underlie ADE: involvement of complement component C1q and its receptor (Ebola virus), antibody‐mediated modulation of the interaction between viral protein and its coreceptor (human immunodeficiency virus) and suppression of cellular antiviral genes by the replication of viruses entering cells via ADE (Ross River virus). Since ADE is exploited by a variety of viruses and has been associated with disease exacerbation, it may have broad relevance to the pathogenesis of viral infection and antiviral strategies. 

Wan, Yushun, Jian Shang, Shihui Sun, Wanbo Tai, Jing Chen, Qibin Geng, Lei He et al. "Molecular mechanism for antibody-dependent enhancement of coronavirus entry." Journal of virology 94, no. 5 (2020).

Abstract

Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.

IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.

Wang, Sheng-Fan, Sung-Pin Tseng, Chia-Hung Yen, Jyh-Yuan Yang, Ching-Han Tsao, Chun-Wei Shen, Kuan-Hsuan Chen et al. "Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins." Biochemical and biophysical research communications." 451, no. 2 (2014): 208-214.

 

Wang, Qidi, Lianfeng Zhang, Kazuhiko Kuwahara, Li Li, Zijie Liu, Taisheng Li, Hua Zhu et al. "Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates." ACS infectious diseases 2, no. 5 (2016): 361-376.

Classen, J. Barthelow. "Review of vaccine induced immune overload and the resulting epidemics of type 1 diabetes and metabolic syndrome, emphasis on explaining the recent accelerations in the risk of prediabetes and other immune mediated diseases." Molecular and Genetic Medicine (2014): 1747-0862.

 

Key Points

1) “There has been an epidemic of inflammatory diseases that has paralleled the epidemic on iatrogenic immune stimulation with vaccines.” 2) “Extensive evidence links vaccine induced immune over load with the epidemic of type-1 diabetes.” 3) “Obesity, type-2 diabetes and other components of metabolic syndrome are highly associated with immunization and may be manifestations of the negative feedback loop of the immune system reacting to the immune overload.” 4) “Twenty years ago it was predicted that a massive increase in immunization would result in a massive increase in people with chronic immune related diseases like type-1 diabetes, autoimmune diseases, and asthma.” 5) Since 1999, US children are scheduled to routinely receive over 80 additional vaccines over their childhood. “The increase in immunization has been followed by a huge increase in inflammation associated disorders. Diseases like autism, type-1 diabetes, asthma, food allergies, many autoimmune diseases, obesity, type-2 diabetes, NASH [a type of fatty liver disease] and metabolic syndrome have increased many fold in children.” 6) There is “evidence that vaccines are responsible for the epidemics of both autoimmune diseases such as type-1 diabetes as well as the epidemic of type-2 diabetes, obesity and metabolic syndrome.” 7) In order to induce a protective response in most children, vaccines will over stimulate the immune response in children with the weakest immune system. “The process of over stimulating the immune system time and time again increases the risk of inflammatory diseases like autoimmune diseases, and allergies which cause even more inflammation.” 8) “Evidence that vaccines cause type-1 diabetes has been well established.” “Discontinuation of vaccines has been repeatedly shown to be followed by declines in the rates of type-1 diabetes.” 9) There exists a theory that the obesity epidemic is caused by the physiological response to immune stimulation and the resulting cortisol production in a negative feedback loop with the immune system. Elevated cortisol in response to immune activation inflammation is linked to obesity, type-2 diabetes, insulin resistance, and hypertension. 10) “The theory of vaccine induced immune overload explains the parallel epidemics of multiple different autoimmune diseases.” 11) The diagnosis of autism is epidemic. “Many cases of autism have a strong inflammatory component and the epidemic has already been linked to vaccine induced overload.” 12) Paralleling the increased number of vaccines, this author references: • Increased incidence of autism. • Increased diabetes. • Increased autoimmune diseases. • Increased attention deficit syndrome. • Increase in many inflammatory mediated diseases. • The incidence of psoriasis has doubled in children. • The incidence of inflammatory bowel disease is increasing rapidly in children. • An increased risk of asthma. • A rise in food related allergens. • “Peanut allergy has tripled in children since 1997.” • Celiac disease has increased substantially. 13) “There has been an epidemic of inflammatory diseases that has paralleled the epidemic on iatrogenic immune stimulation with vaccines.”

An increasing number of cases of POI post-HPV4 are being reported. Possible mechanisms for the suspected effect of HPV on female reproductive function are a toxic effect or an autoimmune response. The trigger could be the vaccine immunogen contents or the adjuvants, the latter are used to increase the immune reaction. The adjuvant in HPV4 contains aluminum. Animal models have shown aluminum exposure to inhibit expression of female reproductive hormones and to induce histologic changes in the ovaries. Specific genetic compositions may be more susceptible to developing an autoinflammatory syndrome after exposure to an environmental factor.

 

Little, Deirdre Therese, and Harvey Rodrick Grenville Ward. "Adolescent premature ovarian insufficiency following human papillomavirus vaccination: a case series seen in general practice." Journal of investigative medicine high impact case reports 2, no. 4 (2014): 2324709614556129.

 

Abstract 

Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV) vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and post-licensure studies. Post marketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence.

 

Little, Deirdre Therese, and Harvey Rodrick Grenville Ward. "Premature ovarian failure 3 years after menarche in a 16-year-old girl following human papillomavirus vaccination." Case Reports 2012 (2012): bcr2012006879.

 

Summary

Premature ovarian failure in a well adolescent is a rare event. Its occurrence raises important questions about causation, which may signal other systemic concerns. This patient presented with amenorrhoea after identifying a change from her regular cycle to irregular and scant periods following vaccinations against human papillomavirus. She declined the oral contraceptives initially prescribed for amenorrhoea. The diagnostic tasks were to determine the reason for her secondary amenorrhoea and then to investigate for possible causes of the premature ovarian failure identified. Although the cause is unknown in 90% of cases, the remaining chief identifiable causes of this condition were excluded. Premature ovarian failure was then notified as a possible adverse event following this vaccination. The young woman was counselled regarding preservation of bone density, reproductive implications and relevant follow-up. This event could hold potential implications for population health and prompts further inquiry

Pellegrino, Paolo, Carla Carnovale, Valentina Perrone, Dionigi Salvati, Marta Gentili, Tatiana Brusadelli, Marco Pozzi, Stefania Antoniazzi, Emilio Clementi, and Sonia Radice. "On the association between human papillomavirus vaccine and primary ovarian failure." American Journal of Reproductive Immunology 71, no. 4 (2014): 293-294.

 

Tomljenovic, Lucija, and Christopher A. Shaw. "Adverse reactions to human papillomavirus vaccines." Vaccines and Autoimmunity (2015): 163-174.

 

Summary

This chapter reviews the data from numerous reports substantiating the link between adverse immune reactions and human papillomavirus (HPV) vaccines. It discusses the results from safety clinical trials on HPV vaccines. In their 2008 pre‐licensure analysis of ADRs of potential autoimmune etiology in a large integrated safety database of ASO4 adjuvanted vaccines (including Cervarix), Verstraeten et al. pointed out that “It is important to note that none of these studies were set up primarily to study autoimmune disorders.” Large post‐licensure epidemiological studies assessing the safety of Gardasil likewise failed to identify any significant autoimmune safety concerns. Post‐vaccination adverse immune phenomena can have long latency periods. The human clinical trial data for the two HPV vaccines currently on the market reveal a troubling safety profile that requires an accurate reevaluation of the risks and benefits.

 

Tomljenovic, Lucija, and C. A. Shaw. "Death after quadrivalent human papillomavirus (HPV) vaccination: causal or coincidental." Pharmaceut Reg Affairs S 12 (2012): 2.

 

Abstract:

Background: The proper understanding of a true risk from vaccines is crucial for avoiding unnecessary adverse reactions (ADRs). However, to this date no solid tests or criteria have been established to determine whether adverse events are causally linked to vaccinations. 

Objectives: This research was carried out to determine whether or not some serious autoimmune and neurological ADRs following HPV vaccination are causal or merely coincidental and to validate a biomarker-based immunohistochemical (IHC) protocol for assessing causality in case of vaccination-suspected serious adverse neurological outcomes.

Methods: Post-mortem brain tissue specimens from two young women who suffered from cerebral vasculitis type symptoms following vaccination with the HPV vaccine Gardasil were analysed by IHC for various immunoinflammatory markers. Brain sections were also stained for antibodies recognizing HPV-16L1 and HPV-18L1 antigen which are present in Gardasil. Results: In both cases, the autopsy revealed no anatomical, microbiological nor toxicological findings that might have explained the death of the individuals. In contrast, our IHC analysis showed evidence of an autoimmune vasculitis potentially triggered by the cross-reactive HPV-16L1 antibodies binding to the wall of cerebral blood vessels in all examined brain samples. We also detected the presence of HPV-16L1 particles within the cerebral vasculature with some HPV-16L1 particles adhering to the blood vessel walls. HPV-18L1 antibodies did not bind to cerebral blood vessels nor any other neural tissues. IHC also showed increased T-cell signalling and marked activation of the classical antibody-dependent complement pathway in cerebral vascular tissues from both cases. This pattern of complement activation in the absence of an active brain infection indicates an abnormal triggering of the immune response in which the immune attack is directed towards self-tissue. 

Conclusions: Our study suggests that HPV vaccines containing HPV-16L1 antigens pose an inherent risk for triggering potentially fatal autoimmune vasculopathies. Practice implications: Cerebral vasculitis is a serious disease which typically results in fatal outcomes when undiagnosed and left untreated. The fact that many of the symptoms reported to vaccine safety surveillance databases following HPV vaccination are indicative of cerebral vasculitis, but are unrecognized as such (i.e., intense persistent migraines, syncope, seizures, tremors and tingling, myalgia, locomotor abnormalities, psychotic symptoms and cognitive deficits), is a serious concern in light of the present findings. It thus appears that in some cases vaccination may be the triggering factor of fatal autoimmune/neurological events. Physicians should be aware of this association

 

Tomljenovic, Lucija, Serena Colafrancesco, Carlo Perricone, and Yehuda Shoenfeld. "Postural orthostatic tachycardia with chronic fatigue after HPV vaccination as part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants” case report and literature review." Journal of investigative medicine high impact case reports 2, no. 1 (2014): 2324709614527812.

 

Abstract

We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud’s syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient), a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

Tetanus Vaccine Description and Reactions

In the U.S. today, tetanus vaccine is administered only in a combination shot (DTaP, DT, Tdap, Td) that contains vaccines for tetanus (T), diphtheria (D) and possibly pertussis (whooping cough) (P). The CDC’s Advisory Committee on Immunization Practices (ACIP) currently recommends administration of a tetanus containing vaccine (DTaP) at two, four, and six months old; between 15 and 18 months old; and between four and six years old. Another booster dose is recommended at 11-12 years of age (Tdap). After a booster dose of Tdap vaccine, booster doses with tetanus - diphtheria toxoid vaccine (Td) are recommended every ten years throughout a person’s life. While the ACIP also recommends that pregnant women receive a dose of Tdap vaccine during each pregnancy, between 27- and 36-weeks gestation, regardless of a previous history of Tdap vaccine, this recommendation contradicts the information provided by the vaccine manufacturers. Boostrix vaccine is approved to be administered only as a single dose and the Adacel product insert states that a second dose of Adacel vaccine may be administered if there has been at least an 8-year interval between the first Tdap dose. The product insert of both Boostrix and Adacel, the two available FDA licensed Tdap vaccines, also state that there are “no adequate and well-controlled studies” on the use of Tdap vaccine in pregnant women. 

The tetanus toxoid vaccine (TT) was developed in 1924 and became commercially available for use in the United States in 1938. Prior to 1960, the tetanus toxoid (TT) was primarily used, however in the 1960’s, the use of the combination tetanus- diphtheria toxoid vaccine (Td) became more prevalent. In 2013, the single antigen tetanus toxoid vaccine (TT) was discontinued in the United States. The tetanus toxoid vaccine is available only in combination with other routinely administered vaccines and most frequently combined with diphtheria (DT, Td) and acellular pertussis vaccines (DTaP, Tdap). It can also be found in combination with vaccines for polio, haemophilus influenzae B (HIB), and hepatitis B (see below for descriptions).

 

Tetanus Toxoid Vaccines Licensed for Use in the U.S.

The U.S. FDA has approved twelve different combination vaccine that include tetanus toxoid vaccine. There are different rules for use of these vaccines by different aged groups.

Following is a list of currently available vaccine combination shots that contain tetanus toxoid vaccine with links to the manufacturer product inserts (click on the name of the product):

  • Infanrix, a 3 in 1 combination shot containing diphtheria, tetanus toxoids, and acellular pertussis vaccine for children under 7 years of age. It is manufactured by GlaxoSmithKline.

  • DAPTACEL, a 3 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis vaccine for children under 7 years of age. It is manufactured by Sanofi Pasteur Ltd.

  • Pediarix, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, hepatitis B recombinant and inactivated poliovirus vaccines for children under 7 years of age. It is manufactured by GlaxoSmithKline.

  • Kinrix, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoids, acellular pertussis, and inactivated poliovirus vaccines for children 4 to 6 years old. It is manufactured by GlaxoSmithKline.

  • Quadracel, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoid, acellular pertussis, and inactivated poliovirus vaccine for children 4 to 6 years old. It is manufactured by Sanofi Pasteur

  • Pentacel, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine for children under four years old. It is manufactured by Sanofi Pasteur Ltd.

  • VAXELIS, a 6 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus b conjugate, and hepatitis B recombinant vaccine for children under 5 years of age. It is manufactured by MCM Vaccine Company. (Not currently available for use)

  • Diphtheria and Tetanus Toxoid Adsorbed, a 2 in 1 combination shot containing diphtheria and tetanus toxoid for children under seven years old. It is manufactured by Sanofi Pasteur Ltd

  • Adacel, a 3 in 1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine for those 10 years or older. It is manufactured by Sanofi Pasteur Ltd.

  • Boostrix, a 3 in 1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine for those 10 years or older. It is manufactured by GlaxoSmithKline.

  • TDVAX, a 2 in 1 combination shot containing tetanus and diphtheria toxoid for those 7 years of age or older. It is manufactured by MassBiologics

  • TENIVAC, a 2 in 1 combination shot containing tetanus and diphtheria toxoid for those 7 years of age or older. It is manufactured by Sanofi Pasteur

 

Combination Vaccines

There are some doctors who limit the numbers of vaccines given simultaneously on the same day and will work as partners with parents to choose certain vaccine products and develop individualized schedules for vaccination. If you want your child to receive tetanus vaccine but would prefer a 3 in 1 combination shot (diphtheria, tetanus, and pertussis) rather than a 4 in 1 or 5 in 1 combination shot, talk with your doctor.

If your doctor or the nurse administering vaccines refuses to have a discussion with you about vaccine products or schedules, you may want to consider consulting one or more other trusted health care professionals before making a vaccine decision.

Not all tetanus-containing vaccines have been studied in clinical trials to prove the safety and effectiveness of giving the shot simultaneously with other licensed vaccines. Check the product inserts for more information about administering vaccines at the same time with other vaccines.

Source: NVIC.ORG

Articles DPT Vaccine Reactions

Cody, Christopher L., Larry J. Baraff, James D. Cherry, S. Michael Marcy, and Charles R. Manclark. "Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children." Pediatrics 68, no. 5 (1981): 650-660.

 

Abstract

In 784 DT and 15,752 DTP immunizations given to children 0 to 6 years of age who were prospectively studied for reactions occurring within 48 hours following immunization, minor reactions were significantly more frequent following DTP vaccine. The ratio of reaction rates associated with DTP and DT immunizations (DTP/DT) for selected local and systemic reactions was as follows: local redness, 37.4%/7.6%; local swelling, 40.7%/7.6%; pain, 50.9%/9.9%; fever, 31.5%/14.9%; drowsiness, 31.5%/14.9%; fretfulness, 53.4%/22.6%; vomiting, 6.2%/2.6%; anorexia, 20.9%/7.0% and persistent crying, 3.1%/0.7%. Following DTP immunization nine children developed convulsions and nine developed hypotonic hyporesponsive episodes. No sequelae were detected following these reactions.

Sun, Yuelian, Jakob Christensen, Anders Hviid, Jiong Li, Peter Vedsted, Jørn Olsen, and Mogens Vestergaard. "Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B." Jama 307, no. 8 (2012): 823-831.

 

Abstract

Context Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002.

Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months.

Design, Setting, and Participants A population-based cohort study of 378 834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort.

Main Outcome Measures Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study.

Results A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100 000 person-days), 32 children after the second (1.3 per 100 000 person-days), and 201 children after the third (8.5 per 100 000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100 000 person-days), 12 children after the second (5.7 per 100 000 person-days), and 27 children after the third (13.1 per 100 000 person-days) vaccinations. The relative incidences from the SCCS study design were similar to the cohort study design. Within 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15 months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000 person-years). After vaccination, children had a lower risk of epilepsy between 3 and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children.

Conclusions DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy.

Studies have reported increased risks of febrile seizures shortly after administration of whole-cell pertussis vaccine, as would be expected since the whole-cell pertussis vaccine often causes fever. Whole-cell pertussis vaccine has also been associated with serious neurological illnesses characterized by seizures and intellectual impairment, but recent studies indicate that the vaccination only triggers an earlier onset of severe epileptic encephalopathy in children with sodium channel gene mutations. The acellular pertussis vaccine has replaced the whole-cell pertussis vaccine in most countries because the efficacy of the acellular vaccine is comparable with the whole-cell vaccine and it has substantially fewer adverse effects, including fever. Previous randomized controlled trials did not reveal differences in the risk of seizures after acellular pertussis vaccination compared with whole-cell pertussis vaccination, but the trials were not powered to detect rare adverse effects. A study from the United Kingdom found a 2-fold higher risk of seizures on the day of the diphtheria-tetanus toxoids-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination, and a study from the United States found a 30% higher risk of seizures on the day of the first DTaP vaccination. However, these estimates did not reach statistical significance and the studies did not distinguish between afebrile and febrile seizures. We examined the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination in a large nationwide, population-based cohort study in Denmark.

 

Measles, Mumps, Rubella Vaccine Description and Reactions

Measles vaccine is a weakened (attenuated) form of the live measles virus. There are 2 vaccines currently available for use in the U.S.: Merck's MMRII, which contains Measles, Mumps and Rubella Vaccine, Live; and Merck's Proquad (MMRV), which contains Measles, Mumps, Rubella and Varicella, Live.  

Merck’s MMRII is licensed and recommended for individuals aged 12 months or older. It is a live attenuated virus vaccine propagated in chick embryo cells and cultured with Jeryl Lynn live attenuated virus mumps and Meruvax II, a live attenuated rubella virus vaccine propagated in WI-38 human diploid lung fibroblasts. The WI-38 human diploid cell line was derived from the lung tissue of a three-month human female embryo. The growth medium used was salt solution and 10 percent calf (bovine) serum. 

Merck's ProQuad is licensed and recommended for individuals aged 12 months to 12 years of age. ProQuad (MMR-V -Measles, Mumps, Rubella and Varicella Virus Vaccine Live) is a combined, attenuated, live virus vaccine containing measles, mumps, rubella, and varicella viruses. ProQuad is a sterile lyophilized preparation of the components of M-M-R II (Measles, Mumps, and Rubella Virus Vaccine Live): Measles Virus Vaccine Live, and Varicella Virus Vaccine Live (Oka/Merck), the Oka/Merck strain of varicella-zoster virus propagated in MRC-5 cells. MRC-5 cells are derived from a cell line developed in 1966 from lung tissue of a 14-week aborted fetus and contains viral antigens. 

The growth medium for measles and mumps in both MMRII and ProQuad is a buffered salt solution containing vitamins and amino acids and it is supplemented with fetal bovine serum containing sucrose, phosphate, glutamate, recombinant human albumin, and neomycin. The growth medium for rubella is a buffered salt solution containing vitamins and amino acids and supplemented with fetal bovine serum containing recombinant human albumin and neomycin. Sorbitol and hydrolyzed gelatin stabilizer are added to the individual virus harvests. In the ProQuad vaccine, the Oka/Merck strain of the live attenuated varicella virus, initially obtained from a child with wild-type varicella, introduced into human embryonic lung cell cultures, adapted to and propagated in embryonic guinea pig cell cultures and human diploid cell cultures (WI-38), is then added to the MMRII component.

According to Merck, both MMRII and ProQuad vaccines are screened for adventitious agents. Each dose of MMRII contains sorbitol, sodium phosphate, sucrose, sodium chloride, hydrolyzed gelatin, recombinant human albumin, fetal bovine serum, other buffer and media ingredients and neomycin. Each dose of ProQuad contains sucrose, hydrolyzed gelatin, sorbitol, MSG, sodium phosphate, human albumin, sodium bicarbonate, potassium phosphate and chloride, neomycin, bovine calf serum, chick embryo cell culture, WI-38 human diploid lung fibroblasts and MRC-5 cells. 

The MMRII vaccine product information inserts states that the MMRII vaccine should be given one month before or one month after any other live viral vaccines. The ProQuad vaccine product information insert states that one month should lapse between administration of ProQuad and another measles containing vaccine such as MMRII and at least three months should lapse between ProQuad and any varicella containing vaccine. 

The CDC currently recommends that children receive two doses of a measles containing vaccine, with the first dose administered between 12-15 months, and the second dose between 4-6 years. The CDC also recommends that individuals born after 1957 and have no laboratory evidence of immunity or documentation of vaccination should receive at least one dose of MMR vaccine. Two doses of MMR vaccine are also recommended for healthcare personnel, students entering college and other post-high school educational institutions, and international travelers. 

MMR vaccination is recommended by the CDC for infants between 6 and 11 months of age who may be traveling internationally; however, ProQuad and MMRII are only FDA approved for use in children 12 months and older. The MMRII vaccine product insert states that the effectiveness and safety of MMRII has not been established in children between 6 and 11 months and if administered to this population, antibodies may not develop. According to the CDC, an infant vaccinated prior to 12 months of age will still require two additional doses of MMR vaccine.

Source: NVIC.ORG 

Guillain-Barré syndrome, an autoimmune polyneuropathy, has become the most common cause of acute generalized paralysis and is thought to be immune-mediated. It is preceded by upper respiratory or gastrointestinal infection in about two-thirds of cases and is associated with some viral infections, including influenza. GBS affects individuals of all ages but is rare in infancy. GBS has been attributed to certain vaccinations, particularly, in relation to monovalent or combination measles, mumps, and rubella vaccines, influenza vaccine, oral polio vaccine, diphtheria and tetanus toxoids. GBS has also been associated with the 1976 swine-influenza vaccine. Thereafter, some studies have shown an increased risk of GBS following receipt of seasonal and 2009 H1N1 monovalent influenza vaccines. Studies over the years have also shown an increased risk of GBS following influenza infection, and the magnitude of risk is several times greater than that following influenza vaccination.

Autism is a complex disorder of the central nervous system (CNS), manifesting both neurological as well as behavioral impairments. The disorder causes severe deficits of higher mental functions such as social interaction, language, communication, imagination, and cognition. The etiology and pathogenesis of the disorder is not well known or established. Current theories include genetic factors, immune factors, viral factors, neural factors, and yet other unidentified factors.

Because viruses are common trigger agents for autoimmune diseases such as GBS, it has also been proposed that a virus-induced autoimmune response may play a causal role in autism. Vaccination of the measles virus, mumps virus, and rubella virus has been implicated as a cause or co-cause of autism. In particular, elevated levels of measles antibodies in autistic children are a possible consequence of a misguided immune response to measles vaccine.

Articles MMR Vaccine Reactions

Dourado, Ines, Sergio Cunha, Maria da Gloria Teixeira, C. Paddy Farrington, Ailton Melo, Rita Lucena, and Maurício L. Barreto. "Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs." American journal of epidemiology 151, no. 5 (2000): 524-530.

 

Abstract

A mass immunization campaign with a Urabe-containing measles-mumps-rubella vaccine was carried out in 1997 in the city of Salvador, northeastern Brazil, with a target population of children aged 1-11 years. There was an outbreak of aseptic meningitis following the mass campaign. Cases of aseptic meningitis were ascertained through data collected from the records of children admitted to the local referral hospital for infectious diseases between March and October of 1997, using previously defined eligibility criteria. Vaccination histories were obtained through home visits or telephone calls. Eighty-seven cases fulfilled the study criteria. Of those, 58 cases were diagnosed after the vaccination campaign. An elevated risk of aseptic meningitis was observed 3 weeks after Brazil's national vaccination day compared with the risk in the prevaccination period (relative risk = 14.3; 95% confidence interval: 7.9, 25.7). This result was confirmed by a case series analysis (relative risk = 30.4; 95% confidence interval: 11.5, 80.8). The estimated risk of aseptic meningitis was 1 in 14,000 doses. This study confirms a link between measles-mumps-rubella vaccination and aseptic meningitis. The authors discuss the implications of this for the organization and planning of mass immunization campaigns. 

Miller, Elizabeth, P. Farrington, M. Goldracre, S. Pugh, A. Colville, Audrey Flower, James Nash, Lorna MacFarlane, and Richard Tettmar. "Risk of aseptic meningitis after measles, mumps, and rubella vaccine in UK children." The Lancet 341, no. 8851 (1993): 979-982.

 

Abstract

Cases of aseptic meningitis associated with measles/mumps/rubella vaccine were sought in thirteen UK health districts following a reported cluster in Nottingham which suggested a risk of 1 in 4000 doses, substantially higher than previous estimates based on cases reported by paediatricians (4 per million). Cases were ascertained by obtaining vaccination records of children with aseptic meningitis diagnosed from cerebrospinal fluid samples submitted to Public Health Laboratories or discharged from hospital with a diagnosis of viral meningitis. Both methods identified vaccination 15-35 days before onset as a significant risk factor and therefore indicative of a causal association. With both, half the aseptic meningitis cases identified in children aged 12-24 months were vaccine-associated with onset 15-35 days after vaccine. The study confirmed that the true risk was substantially higher than suggested by case reports from pediatricians, probably about 1 in 11 000 doses. However, the possibility that the aseptic meningitis induced by vaccination was largely asymptomatic and a chance laboratory finding in children investigated for other clinical conditions, particularly febrile convulsions, could not be excluded. Comparison of national reports of virus-positive mumps meningitis cases before and after the introduction of this vaccine indicated that the risk from wild mumps was about 4-fold higher than from vaccine. Altogether, 28 vaccine-associated cases were identified, all in recipients of vaccines containing the Urabe mumps strain. The absence of cases in recipients of vaccine containing the Jeryl Lynn strain, despite its 14% market share, suggested a higher risk from Urabe vaccine. A prospective adverse event surveillance system using the study methods is currently being established to assess the risk, if any, from the Jeryl Lynn strain which is now the only mumps vaccine used in the UK.

 

Articles Measles Vaccine Reactions

Grose, Charles, and Ilya Spigland. "Guillain-Barré syndrome following administration of live measles vaccine." The American journal of medicine 60, no. 3 (1976): 441-443.

 

Abstract

In a 19-month-old girl and a 10-month-old girl the Guillain-Barré syndrome developed within a week after they received, respectively, live measles-rubella vaccine and live measles vaccine. The older child was immune to rubella at the time of vaccination, but both girls demonstrated a primary measles antibody response. Serum obtained during the acute and convalescent stages from the younger child was tested for antibodies against the herpes viruses (herpes simplex, Epstein-Barr virus, cytomegalovirus and varicella-zoster) and found to be negative.

Kawashima, Hisashi, Takayuki Mori, Yasuyo Kashiwagi, Kouji Takekuma, Akinori Hoshika, and Andrew Wakefield. "Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism." Digestive diseases and sciences 45, no. 4 (2000): 723-729.

 

Abstract

It has been reported that measles virus may be present in the intestine of patients with Crohn’s disease. Additionally, a new syndrome has been reported in children with autism who exhibited developmental regression and gastrointestinal symptoms (autistic enterocolitis), in some cases soon after MMR vaccine. It is not known whether the virus, if confirmed to be present in these patients, derives from either wild strains or vaccine strains. In order to characterize the strains that may be present, we have carried out the detection of measles genomic RNA in peripheral mononuclear cells (PBMC) in eight patients with Crohn’s disease, three patients with ulcerative colitis, and nine children with autistic enterocolitis. As controls, we examined healthy children and patients with SSPE, SLE, HIV-1 (a total of eight cases). RNA was purified from PBMC by Ficoll-paque, followed by reverse transcription using AMV; cDNAs were subjected to nested PCR for detection of specific regions of the hemagglutinin (H) and fusion (F) gene regions. Positive samples were sequenced directly, in nucleotides 8393–8676 (H region) or 5325–5465 (from noncoding F to coding F region). One of eight patients with Crohn disease, one of three patients with ulcerative colitis, and three of nine children with autism, were positive. Controls were all negative. The sequences obtained from the patients with Crohn’s disease shared the characteristics with wild-strain virus. The sequences obtained from the patients with ulcerative colitis and children with autism were consistent with being vaccine strains. The results were concordant with the exposure history of the patients. Persistence of measles virus was confirmed in PBMC in some patients with chronic intestinal inflammation.

Landrigen PJ, Witte JJ. 1973. "Neurologic disorders following live measles virus vaccination." Journal of the American Medical Association 223:1459-1462.

 

Abstract

From 1963 through 1971, eighty-four cases of neurologic disorders with onset less than 30 days after live measles-virus vaccination were reported in the United States. Thirteen could be adequately accounted for by causes other than vaccine, and another 11 were uncomplicated febrile convulsions probably related to vaccination. One case met diagnostic criteria for subacute sclerosing panencephalitis. The remaining 59 showed clinical features of encephalitis or encephalopathy. Causes of these cases could not be established, but 45 (76%) had onset between 6 and 15 days after vaccination; this clustering suggests that some may have been caused by vaccine. From 1963 through 1971, 50.9 million doses of measles vaccine were distributed, and, therefore, incidence of the reported neurologic disorders was 1.16 per million doses. Risk of encephalitis following measles infection is one per thousand cases.

Quast, Ute, W. Hennessen, and R. M. Widmark. "Vaccine induced mumps-like diseases." Developments in Biological Standardization 43 (1979): 269.

 

Abstract

Sixteen cases of parotitis and 2 cases of diabetes mellitus after mumps vaccination have been reported since the introduction of the live attenuated mumps vaccine in the F. R. Germany in the fall of 1976. Due to the post-vaccination incubation of 7 to 10 days, support is given to the assumption that these cases are vaccine induced and not coincidental wild virus infections.

 

Articles Mumps Vaccine Reactions

Brown, E. G., J. Furesz, K. Dimock, W. Yarosh, and G. Contreras. "Nucleotide sequence analysis of Urabe mumps vaccine strain that caused meningitis in vaccine recipients." Vaccine 9, no. 11 (1991): 840-842.

 

Abstract

Mumps virus was isolated from the cerebrospinal fluid of eight patients who acquired meningitis within 4 weeks of immunization with live Trivirix vaccine that contains mumps (Urabe Am 9), measles (Schwarz), and rubella (RA 27/3) viruses. Part of the haemagglutinin-neuraminidase (HN) gene from three postvaccination isolates of mumps virus, three wild strains and the Urabe and Jeryl Lynn vaccine strains was cloned following polymerase chain reaction (PCR) amplification, for the purpose of sequence analysis. A 200-nucleotide portion of the cloned HN genes was sequenced and compared to published sequences of two other strains (RW and SBL-1). The postvaccination mumps strains were identical in sequence to Urabe and were distinguishable from the wild and the Jeryl Lynn vaccine strains. Twenty-two out of 200 position were seen to vary among the group of viruses. It was concluded that the Urabe vaccine strain was the cause of postvaccination meningitis. Therefore, with effect from 1990, Trivirix measles, mumps and rubella vaccine is no longer licensed for sale in Canada.

Cizman, M., M. Mozetic, R. Radescek-Rakar, D. Pleterski-Rigler, and M. Susec-Michieli. "Aseptic meningitis after vaccination against measles and mumps." The Pediatric infectious disease journal 8, no. 5 (1989): 302-308.

 

Abstract 

This retrospective study (1979 to 1986) investigated the possible etiologic relationship between vaccination and aseptic meningitis in 115 hospitalized children who became ill within 30 days of vaccination with the Leningrad 3 strain of mumps virus and the Edmonston-Zagreb strain of measles virus. The etiologic viral diagnosis was based on serologic tests and the isolation of virus from cell cultures which distinguished between attenuated and "virulent" mumps virus. The incidence of mumps vaccine-associated meningitis was 1/1000 vaccine recipients. In 92% of children the incubation period was 11 to 25 days and 28% had associated swelling of the salivary glands. Sixteen cases (13.9%) had a positive cerebrospinal fluid culture (attenuated mumps virus, 6 cases; "virulent" mumps virus, 7 cases; echoviruses, 3 cases). Clustering of cases, seasonal occurrence and age of the patients suggested causal relationship with the vaccination in the majority of children. In 4 patients with attenuated virus isolation from cerebrospinal fluid the incubation period ranged from 17 to 20 days. Clinical findings did not differ from natural mumps meningitis. The course was uncomplicated and at discharge the patients had no sequelae. Measles virus was never found as a cause of the meningitis. The mumps vaccine virus should be recognized as one of the causative agents of aseptic meningitis in countries where less attenuated mumps vaccine is used.

 

Sugiura, A., and A. Yamada. "Aseptic meningitis as a complication of mumps vaccination." The Pediatric infectious disease journal 10, no. 3 (1991): 209-213.

Abstract

In 1989 a nationwide surveillance of neurologic complications after the administration of mumps vaccine was conducted in Japan, based on the notification of cases and the testing of mumps viruses isolated from cerebrospinal fluid for their relatedness to the vaccine by nucleotide sequence analysis. Among 630,157 recipients of measles-mumps-rubella trivalent (MMR) vaccine containing the Urabe Am9 mumps vaccine, there were at least 311 meningitis cases suspected to be vaccine-related. In 96 of these 311 cases, mumps virus related to the vaccine was isolated from cerebrospinal fluid. The unusually high incidence may have been partly a result of the adverse media publicity of the problem at the time of surveillance. We analyzed clinical features of 165 and 27 laboratory-confirmed mumps vaccine-related meningitis cases that occurred among the recipients of MMR and monovalent mumps vaccines, respectively, during a 1-year period after the introduction of MMR vaccine. The incidence of vaccine-related meningitis was similar among the recipients of MMR and monovalent Urabe Am9 mumps vaccines. Meningitis was generally mild and there were no sequelae from the illness. The complication was more frequent among male than among female children.

 

da Silveira, Claudio Marcos, Claudete Iris Kmetzsch, Renate Mohrdieck, Alethea Fagundes Sperb, and D. Rebecca Prevots. "The risk of aseptic meningitis associated with the Leningrad-Zagreb mumps vaccine strain following mass vaccination with measles-mumps-rubella vaccine, Rio Grande do Sul, Brazil, 1997." International journal of epidemiology 31, no. 5 (2002): 978-982.

 

Abstract

Background Few data are available on the risk of aseptic meningitis following vaccination with the Leningrad-Zagreb (L-Z) strain of mumps vaccine. In 1997 the mumps vaccine was introduced into the state of Rio Grande do Sul in Brazil through mass vaccination with mumps-measles-rubella (MMR), targeting children aged 1–11 years. Five municipalities used exclusively MMR vaccine containing the L-Z strain of mumps. An outbreak of aseptic meningitis was observed shortly after the mass campaign.

Methods To estimate the risk of aseptic meningitis associated with this strain, we analysed vaccination and meningitis case surveillance data from the selected municipalities. A case of vaccine-associated aseptic meningitis was defined as one with a pleocytosis of 10–1500 leukocytes/ml and occurring within 15–35 days after vaccine receipt.

Results We estimated a risk of 2.9 cases per 10 000 doses of L-Z administered, equivalent to 1 case per 3390 doses administered. The overall risk of aseptic meningitis following the campaign was increased 12.2-fold (95% CI: 6.0–24.7) compared with the same period in 1995–1996. Following the mass campaign, the incidence of mumps declined 93% during 1998–2000.

Conclusions Vaccination with the L-Z strain of mumps vaccine as part of a mass campaign was associated with a significantly increased risk of aseptic meningitis. Decisions about type of mumps vaccine and mumps vaccination strategies must consider vaccine safety issues in addition to other criteria.

 

Articles Rubella Vaccine Reactions

 

Mitchell, Leslie A., Aubrey J. Tingle, Robert Shukin, Jon A. Sangeorzan, Joseph McCune, and Daniel K. Braun. "Chronic rubella vaccine-associated arthropathy." Archives of internal medicine 153, no. 19 (1993): 2268-2274.

Abstract

Rubella immunization or infection is an uncommonly recognized cause of acute, recurrent, or persistent musculoskeletal manifestations. After routine rubella immunization, two women presented with the onset of polyarthralgia, arthritis, maculopapular rash, fever, paresthesia, and malaise with persistent or recurrent manifestations lasting longer than 24 months after vaccination. The patients expressed rubella virus RNA in peripheral-blood leukocytes 10 and 8 months after vaccination, respectively, in contrast to repeated negative results in asymptomatic rubella-immunized controls. One patient developed significantly depressed antibody responses to rubella virus after vaccination and experienced a prolonged clinical improvement after a 3-month course of intravenous immune globulin. The second patient had normal antibody responses to rubella virus and underwent no clinical improvement during or after intravenous immune globulin therapy. Rubella immunization or infection should be considered as additional causative factors in evaluation of acute and continuing musculoskeletal syndromes.

 

Tingle, Aubrey J., Janet K. Chantler, Kees H. Pot, Donald W. Paty, and Denys K. Ford. "Postpartum rubella immunization: association with development of prolonged arthritis, neurological sequelae, and chronic rubella viremia." Journal of Infectious Diseases 152, no. 3 (1985): 606-612.

 

Abstract

Six women developed chronic long-term arthropathy after postpartum immunization against rubella. All individuals developed acute polyarticular arthritis within 12days to three weeks postimmunization and have had continuing chronic or recurrent arthralgia or arthritis for two to seven years after vaccination. Acute neurological manifestations, consisting of carpal tunnel syndrome or multiple paresthesia, developed postvaccination in three women. Two have developed continuing active or chronic recurrent episodes of blurred vision, paresthesia, and painful limb syndromes together with recurrent joint symptoms. Chronic rubella viremia has been detected in peripheral blood mononuclear cell (MNC) populations in five of the six women up to six years after vaccination. In addition, rubella virus was isolated from breast milk MNCs in one individual at nine months postvaccination and from peripheral blood MNCs in two of four breast-fed infants studied at 12-18months of age. Immune responses to rubella virus studied at sequential intervals after vaccination correlated with development of rheumatologic and neurological manifestations.

Diphtheria Vaccine Description and Reactions

  • The vaccine is a “combination” vaccine, meaning it is given together with two or more other vaccines. Check with your health care provider about which vaccine is being administered. See FDA below for information on combination vaccines containing diphtheria.

  • Adverse reactions to combination vaccines include temperature of 105F or higher, collapse/shock, persistent crying, convulsions, coma, uncontrolled epilepsy, progressive encephalopathy, and death. 

  • Transmission of diphtheria can occur in vaccinated individuals who become asymptomatic carriers of the disease because of the vaccine.

  • As with any vaccine, immunity wanes over time. The CDC recommends adults get booster shots every 10 years.

  • Using the MedAlerts search engine, as of March 31, 2020, there have been more than 187,344 reports of diphtheria vaccine reactions, hospitalizations, injuries, and deaths following diphtheria vaccinations made to the federal Vaccine Adverse Events Reporting System (VAERS), including 3,207 related deaths, 22,619 hospitalizations, and 3,292 related disabilities. Over 60% of those diphtheria vaccine-related adverse events occurring in children under six years old. Some of the adverse reactions of the combination vaccines containing diphtheria include temperature of 105 F. or higher, collapse or shock-like state (hypotonic-hyporesponsive episodes), persistent crying lasting 3 hours or more, convulsions with or without fever, and encephalopathy (coma, decreased level of consciousness, prolonged convulsions).

  • As of May 1, 2020, there had been 5,879 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following Diphtheria vaccination, including 867 deaths and 5,012 serious injuries.

 

Source: NVIC.ORG

Articles Diphtheria Vaccine Reactions

Pertussis Vaccine Description and Reactions

 

In the U.S. today, pertussis vaccine is administered only in a combination shot (DTaP, Tdap) that contains vaccines for diphtheria (D), tetanus (T), and pertussis (whooping cough) (P). The CDC’s Advisory Committee on Immunization Practices (ACIP) currently recommends administration of a pertussis containing vaccine (DTaP) at two, four, and six months old; between 15 and 18 months old; and between four and six years old. Another booster dose is recommended at 12-13 years of age (Tdap).1 While the ACIP also recommends that pregnant women receive a dose of Tdap vaccine during each pregnancy, between 27 and 36 weeks gestation, regardless of a previous history of Tdap vaccine,2 this recommendation contradicts the information provided by the vaccine manufacturers. The product insert of both Boostrix and Adacel, the two available Tdap vaccines in the U.S., state that the safety and effectiveness of vaccination has “not been established in pregnant women”.4

There are various combination shots that bundle diphtheria, tetanus and pertussis vaccines with vaccines for polio, haemophilus influenza B (HIB, and hepatitis B (see below for descriptions).

The whole cell pertussis vaccine was created in 1912 and licensed in 1914. In the 1940’s, the pertussis vaccine was combined with diphtheria and tetanus to become the DPT vaccine and licensed for routine use.5 This vaccine was replaced with a purified, less reactive acellular DTaP vaccine in 1996.6 (DPT was available in some doctor’s offices in the U.S. until about 1999). DPT is still given to infants and children in many developing countries because it costs only pennies to manufacture a dose.7

Pertussis Vaccine Ingredients

The whole cell pertussis vaccine (DPT) is not currently used in the U.S. but remains in use in many developing countries. The whole DPT vaccine contains whole B. pertussis bacteria that is heated and washed with formaldehyde,8 and contains neurotoxic aluminum9 and mercury along with shock-inducing endotoxin,11 12 and brain damaging bioactive pertussis toxin. 

The purified DTaP/Tdap vaccines are packaged in single dose vials and have been given to American babies since the late 1990’s. These vaccines contain reduced bioactive pertussis toxin, less endotoxin, and either no or reduced (trace amounts) of mercury, along with an aluminum adjuvant. 

Depending upon the vaccine manufacturer, shots containing pertussis vaccine may contain varying amounts of inactivated pertussis toxin, filamentous hemagglutinin (FDA), pertactin, fimbriae, formaldehyde, polysorbate 80 (Tween 80), gluteraldehyde, 2-phenoxoyethanol, aluminum and thimerosal (mercury).17

Other ingredients are included in larger combination shots that bundle pertussis, tetanus and diphtheria vaccines with polio, hepatitis B and/or HIB vaccines. See each manufacturer product insert for a list of vaccine ingredients.18

Read the Product Information Insert

NVIC strongly recommends reading the vaccine manufacturer product information insert before you or your child receives any vaccine, including a shot containing pertussis vaccine. Product inserts are published by drug companies making vaccines and list important information about vaccine ingredients, reported health problems (adverse events) associated with the vaccine, and directions for who should and should not get the vaccine.

Links to pertussis-containing product inserts are available below or you can ask your doctor to give you a copy of the vaccine product insert to read before you or your child is vaccinated. It is best to ask your doctor for a copy of the product inserts for the vaccines you or your child is scheduled to receive well in advance of the vaccination appointment.

Pertussis Vaccines Licensed for Use in the U.S.

The U.S. Food and Drug Administration and U.S. Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control (CDC) have approved nine different combination shots that include acellular pertussis vaccine. There are different rules for use of these vaccines by different aged groups.

Following is a list of currently available vaccine combination shots that contain pertussis vaccine with links to the manufacturer product inserts (click on the name of the product):

  • Infanrix, a 3 in 1 combination shot containing diphtheria, tetanus toxoids, and acellular pertussis vaccine for children under 7 years of age. It is manufactured by GlaxoSmithKline.

  • Daptacel, a 3 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis vaccine for children under 7 years of age. It is manufactured by Sanofi Pasteur Ltd.

  • Pediarix, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, hepatitis B recombinant and inactivated poliovirus vaccines for children under 7 years of age. It is manufactured by GlaxoSmithKline.

  • Kinrix, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoids, acellular pertussis and inactivated poliovirus vaccines for children 4 to 6 years old. It is manufactured by GlaxoSmithKline.

  • Quadracel, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoid, acellular pertussis and inactivated poliovirus vaccine for children 4 to 6 years old. It is manufactured by Sanofi Pasteur

  • Pentacel, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccines for children under four years old. It is manufactured by Sanofi Pasteur Ltd.

  • VAXELIS, a 6 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, Inactivated Poliovirus, Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine for children 6 weeks through 4 years of age. It is manufactured by MCM Vaccine Company.

  • Adacel, a 3 in 1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine for those 11 years or older. It is manufactured by Sanofi Pasteur Ltd.

  • Boostrix, a 3 in 1 combination booster shot containing tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine for those 10 years or older. It is manufactured by GlaxoSmithKline.

 

Combination Vaccines

There are some doctors who limit the numbers of vaccines given simultaneously on the same day and will work as partners with parents to choose certain vaccine products and develop individualized schedules for vaccination. If you want your child to receive pertussis vaccine but would prefer a 3 in 1 combination shot (diphtheria, tetanus, pertussis) rather than a 4 in 1 or 5 in 1 combination shot, talk with your doctor.

If your doctor or the nurse administering vaccines refuses to have a discussion with you about vaccine products or schedules, you may want to consider consulting one or more other trusted health care professionals before making a vaccine decision.

Not all pertussis-containing vaccines have been studied in clinical trials to prove the safety and effectiveness of giving the shot simultaneously with other licensed vaccines. Check the product inserts for more information about administering vaccines at the same time with other vaccines.

Source: NVIC.ORG

 

Articles Pertussis Vaccine Reactions

 

Kulenkampff, M., J. S. Schwartzman, and J. Wilson. "Neurological complications of pertussis inoculation." Archives of disease in childhood 49, no. 1 (1974): 46-49.

Abstract

Childhood Neurological complications of pertussis inoculation. Findings are presented in 36 children, seen in the past 11 years, who are believed to have suffered from neurological complications of pertussis inoculation (given as triple vaccine). The clustering of complications in the first 24 hours after inoculation suggests a causal rather than a coincidental relation. Possible contributory factors were present in one-third of patients studied and support the view that idiosyncratic features are present in the patients, not the vaccine. A prospective review is urged. It is recommended that pertussis vaccine should not be given to patients with a history of fits, or a family history of fits in first-degree relatives, or to those who have had a reaction to previous inoculations, those who have had recent intercurrent infection, or those with presumed neurological deficit.

 


Miller, David L., E. M. Ross, R. Alderslade, M. H. Bellman, and N. S. Rawson. "Pertussis immunisation and serious acute neurological illness in children." Br Med J (Clin Res Ed) 282, no. 6276 (1981): 1595-1599.

 

Abstract 

The first 1000 cases notified to the National Childhood Encephalopathy Study were analysed. The diagnoses included encephalitis/encephalopathy, prolonged convulsions, infantile spasms, and Reye's syndrome. Eighty-eight of the children had had a recent infectious disease, including 19 with pertussis. Only 35 of the notified children (3.5%) had received pertussis antigen within seven days before becoming ill. Of 1955 control children matched for age, sex, and area of residence, 34 (1.7%) had been immunized with pertussis vaccine within the seven days before the date on which they became of the same age as the corresponding notified child. The relative risk of a notified child having had pertussis immunization within that time interval was 2.4 (p less than 0.001). Of the 35 notified children, 32 had no previous neurological abnormality. A year later two had died, nine had developmental retardation, and 21 were normal. A significance association was shown between serious neurological illness and pertussis vaccine, though cases were few and most children recovered completely.

 

Stewart, G. T. "Toxicity of pertussis vaccine: frequency and probability of reactions." Journal of Epidemiology & Community Health 33, no. 2 (1979): 150-156.

 

Abstract

From a file of 1127 children in whom signs of brain damage were reported after injections of vaccines containing pertussis antigen, the first 197 cases with good documentation of events were chosen for further study. In these children, 291 reactions had been reported, usually of screaming attacks (68), convulsions (87), collapse (17), or one or more of these signs (99), within 24 hours of injection. Subsequently 165 children became mentally defective and 102 had further convulsions. In 129 (65%), contraindications to vaccination were present ab initio and in 25, subsequent injections were given despite reactions to a previous injection or injections.

From a mathematical model constructed from data in published reports, it is calculated that the frequency of convulsions appears to be higher by 2: 1 in vaccinated than in unvaccinated infants. In children subject to febrile or other convulsions, the frequencies may be of the same order but a second convulsion occurring only after a second or subsequent injection of vaccine is unlikely to be due to chance.

The pattern of reactions and sequence of events observed in the present study and in published reports suggest an association between certain reactions to pertussis vaccine and subsequent severe brain damage, the incidence of which appears to be not less than one per fifty thousand children vaccinated during the last 20 years of mass vaccination in the United Kingdom.

 

Sun, Yuelian, Jakob Christensen, Anders Hviid, Jiong Li, Peter Vedsted, Jørn Olsen, and Mogens Vestergaard. "Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B." Jama 307, no. 8 (2012): 823-831.

 

Abstract

Context Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002.

Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months.

Design, Setting, and Participants A population-based cohort study of 378 834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort.

Main Outcome Measures Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study.

Results A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100 000 person-days), 32 children after the second (1.3 per 100 000 person-days), and 201 children after the third (8.5 per 100 000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100 000 person-days), 12 children after the second (5.7 per 100 000 person-days), and 27 children after the third (13.1 per 100 000 person-days) vaccinations. The relative incidences from the SCCS study design were similar to the cohort study design. Within 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15 months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000 person-years). After vaccination, children had a lower risk of epilepsy between 3 and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children.

Conclusions DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy.

Studies have reported increased risks of febrile seizures shortly after administration of whole-cell pertussis vaccine, as would be expected since the whole-cell pertussis vaccine often causes fever. Whole-cell pertussis vaccine has also been associated with serious neurological illnesses characterized by seizures and intellectual impairment, but recent studies indicate that the vaccination only triggers an earlier onset of severe epileptic encephalopathy in children with sodium channel gene mutations. The acellular pertussis vaccine has replaced the whole-cell pertussis vaccine in most countries because the efficacy of the acellular vaccine is comparable with the whole-cell vaccine and it has substantially fewer adverse effects, including fever. Previous randomized controlled trials did not reveal differences in the risk of seizures after acellular pertussis vaccination compared with whole-cell pertussis vaccination, but the trials were not powered to detect rare adverse effects. A study from the United Kingdom found a 2-fold higher risk of seizures on the day of the diphtheria-tetanus toxoids-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccination, and a study from the United States found a 30% higher risk of seizures on the day of the first DTaP vaccination. However, these estimates did not reach statistical significance and the studies did not distinguish between afebrile and febrile seizures. We examined the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination in a large nationwide, population-based cohort study in Denmark.

Hepatitis B Vaccine Description and Reactions

There are six recombinant hepatitis B vaccines approved by the FDA for use in the U.S.: Engerix-B; Recombivax HB; Twinrix (combined with hepatitis A); Pediarix (combined with diphtheria and tetanus toxoids, acellular pertussis adsorbed, and inactivated poliovirus); and HEPLISAV-B, recombinant adjuvanted vaccine, recommended for use in adults by the CDC in 2018. HEPLISAV-B, a recombinant, adjuvanted hepatitis B vaccine created through genetic engineering of DNA by inserting a segment of the viral gene in a yeast cell, also contains the CpG 1018 adjuvant, not previously used in any vaccine licensed in the U.S. A sixth vaccine, VAXELIS, a 6 in 1 combination vaccine containing diphtheria and tetanus toxoids, acellular pertussis adsorbed, inactivated poliovirus, hepatitis B recombinant, and Hib conjugate vaccine, received FDA approval in December 2018. VAXELIS is expected to be available for use in the United States in 2020, however, at this time the CDC’s Advisory Committee on Immunization Practice (ACIP) has not made any recommendation regarding the use of VAXELIS.

Recombivax HB – According to Merck, Recombivax HB is a recombinant hepatitis B vaccine approved by the FDA for intramuscular administration in both infants and adults. It is derived from hepatitis B virus surface antigen (HBsAg) produced in yeast cells. A portion of the hepatitis B virus gene is cloned into yeast, and the vaccine for hepatitis B is produced from cultures of this recombinant yeast strain using proprietary methods developed in the Merck research laboratories. The antigen is collected and purified from fermentation cultures of a recombinant strain of the yeast Saccharomyces cerevisiae containing the gene for the adw subtype of HBsAg. This fermentation process involves growth of Saccharomyces cerevisiae on a complex fermentation medium which consists of an extract of yeast, soy peptone, dextrose, amino acids, and mineral salts. The HBsAg protein is released from the yeast cells by cell disruption and purified. This purified protein is treated in phosphate buffer with formaldehyde and then coprecipitated with potassium aluminum sulfate and amorphous aluminum hydroxyphosphate sulfate to form the vaccine adjuvant. Each dose of Recombivax HB should contain no more than one percent yeast protein. The vial stopper and the syringe plunger stopper and tip cap contain dry natural latex rubber, which may cause allergic reactions in latex-sensitive individuals.

Recombivax HB is supplied in three formulations. The pediatric/adolescent formulation (approved for birth to age 19) contains 5 mcg of hepatitis B surface antigen in each 0.5ml dose. Adult formulation (> age 20) contains 10 mcg of hepatitis B surface antigen. The dialysis formulation contains 40 mcg of hepatitis B surface antigen in each 1 mL dose.

All formulations contain approximately 0.5 mg of amorphous aluminum hydroxyphosphate sulfate per mL of vaccine. In each formulation, hepatitis B surface antigen is adsorbed onto approximately 0.5 mg of amorphous aluminum hydroxyphosphate sulfate per mL of the vaccine. Recombivax HB contains yeast protein, soy peptone, dextrose, amino acids, mineral salts, potassium aluminum sulfate, amorphous aluminum

hydroxyphosphate sulfate, formaldehyde, phosphate buffer. A series of three doses of the Recombivax HB vaccine is recommended on a one-, two- and six-month schedule.

Animal reproduction studies have not been conducted and it is unknown whether the vaccine can cause fetal harm or affect reproduction. It has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility. 

Engerix B – According to GlaxoSmithKline, Engerix B is a recombinant hepatitis B vaccine approved by the FDA for intramuscular administration in both infants and adults. It is comprised of a suspension of hepatitis B virus surface antigen (HBsAg) and contains purified surface antigen of the hepatitis B virus obtained by culturing genetically engineered Saccharomyces cerevisiae cells (yeast cells), which carry the surface antigen gene of the hepatitis B virus. The HBsAg expressed in the cells is purified and adsorbed on aluminum hydroxide. Engerix B should contain no more than 5 percent yeast protein. The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.

Each 0.5-mL pediatric/adolescent (birth through age 19) dose contains 10 mcg of HBsAg on 0.25 mg aluminum hydroxide.  Each 1 mL adult (> age 20) dose contains 20 mcg of HBsAg adsorbed on 0.5 mg aluminum hydroxide. Engerix B also contains sodium chloride, disodium phosphate dihydrate and sodium dihydrogen phosphate dihydrate. A series of three doses of the Engerix B is recommended on a one-, two- and six-month schedule.

Animal reproduction studies have not been conducted and it is unknown whether the vaccine can cause fetal harm or affect reproduction. It has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility. 

Twinrix - According to GlaxoSmithKline, Twinrix Hepatitis A & Hepatitis B (Recombinant) Vaccine contains the antigen components used to produce Havrix (Hepatitis A Vaccine) and Engerix B Hepatitis B Vaccine (Recombinant). Twinrix is administered intramuscularly and contains inactivated hepatitis A virus (strain HM175) and noninfectious hepatitis B virus surface antigen (HBsAg). The hepatitis A virus is propagated in MRC-5 human diploid cells and inactivated with formalin. The HBsAg is obtained by culturing genetically engineered Saccharomyces cerevisiae yeast cells that contain the surface antigen gene of the hepatitis B virus. Bulk preparations of each antigen are adsorbed onto aluminum salts and then pooled during formulation. The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.

Each 1-mL dose of the vaccine contains 720 ELISA Units of inactivated hepatitis A virus and 20 mcg of recombinant HBsAg protein. It also contains 0.45 mg of aluminum in the form of aluminum phosphate and aluminum hydroxide as adjuvants, amino acids, sodium chloride, phosphate buffer, polysorbate 20, MRC-5 (human diploid cells) proteins, neomycin sulfate, residual formalin, yeast protein and water for Injection.

Animal reproduction studies have not been conducted and it is unknown whether the vaccine can cause fetal harm or affect reproduction. It has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility.

Twinrix is approved in adults > 18 years of age and administered in a series of three doses on a one-, two- and six-month schedule. It is also approved for an accelerated four dose series to be administered on days 0, 7, 21 to 30 with a booster at 12 months. 

Pediarix – According to GlaxoSmithKline, Pediarix and contains Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine.

Each 0.5 mL dose is formulated to contain 25Lf of diphtheria toxoid, 10 Lf of tetanus toxoid, 25 mcg of inactivated pertussis toxin (PT), 25 mcg of filamentous hemagglutinin (FHA), 8 mcg of pertactin (69 kiloDalton outer membrane protein), 10 mcg of HBsAg, 40 D-antigen Units (DU) of Type 1 poliovirus (Mahoney), 8DU of Type 2 poliovirus (MEF-1), and 32 DU of Type 3 poliovirus (Saukett). The diphtheria, tetanus, and pertussis components are the same as those in Infanrix and Kinrix. The hepatitis B surface antigen (HBsAg) is the same as that in Engerix B.

Each 0.5 mL dose contains formaldehyde, glutaraldehyde, aluminum hydroxide, aluminum phosphate, lactalbumin hydrolysate, polysorbate 80, neomycin sulfate, polymyxin B, yeast protein, calf serum, Fenton medium (containing bovine extract), modified Latham medium (derived from bovine casein), modified Stainer-Scholte liquid medium and Vero (monkey kidney) cells.

The tip caps of the prefilled syringes contain natural rubber latex.

Pediarix is approved for use as a three-dose series in infants born of hepatitis B surface antigen (HBsAg)-negative mothers. Pediarix may be given as early as six weeks of age through six years of age (prior to the 7th birthday). 

HEPLISAV-B – According to Dynavax, HEPLISAV-B is a preservative free, .05 mL single dose vial vaccine adjuvanted with 3,000 mcg of CpG 1018, and contains 20 mcg of HBsAg (recombinant Hansenula polymorpha yeast), sodium phosphate, sodium chloride, and polysorbate 80. Vial stoppers are not made with natural rubber latex. 

HEPLISAV-B was approved in 2018 for use in the U.S. for use in adults 18 years of age and older as and intramuscular two dose injection series spaced one month apart. 

There are no clinical studies of HEPLISAV-B in pregnant women and it is not known if the vaccine is excreted in breast milk or would have an impact milk production or breastfed infants. HEPLISAV-B has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility. Animal data on female rats showed no adverse impacts prior to mating, pre- and post-natal development up to the time of weaning, and no fetal malformations. There are also no clinical data on this vaccine’s use in children and adults on hemodialysis.  

VAXELIS is manufactured in partnership by Sanofi Pasteur and Merck (MCM Vaccine Company) and contains Diphtheria and Tetanus Toxoids and Acellular Pertussi Adsorbed, Inactivated Poliovirus, Haemophilus influenzae type b, and Hepatitis B recombinant.  According to the manufacturer’s product insert, each 0.5 mL dose of VAXELIS is formulated to contain 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, acellular pertussis antigens, 20 mcg detoxified pertussis toxin (PT), 20 mcg filamentous hemagglutinin (FHA), 3 mcg pertactin (PRN), 5 mcg fimbriae types 2 and 3 (FIM), inactivated polioviruses (29 D-antigen units (DU) Type 1 Mahoney, 7 DU Type 2 MEF-1, 26 DU Type 3 Saukett, 3 mcg polyribosylribitol phosphate (PRP) of H. influenzae type b bound to 50 mcg of the outer membrane protein complex (OMPC) of Neisseria meningitidis serogroup B, and 10 mcg hepatitis B surface antigen (HBsAg). Each 0.5 mL dose of VAXLEIS contains 319 mcg of aluminum salts as an adjuvant.

Additional ingredients in each 0.5ml dose of VAXELIS includes 319 mcg of aluminum salts as the adjuvant, <0.0056 percent polysorbate 80, less than or equal to 14 mcg residual formaldehyde, less than or equal to 50 ng residual glutaraldehyde, less than or equal to 50 ng residual bovine serum albumin, less than 25 ng of polymyxin B sulfate, less than 5ng of neomycin, less than 200ng of streptomycin sulfate, less than or equal to 0.1ng yeast protein, and less than or equal to 0.125 ng ammonium thiocyanate. VAXELIS does not contain any preservatives. 

VAXELIS is approved for use in infants and children ages 6 weeks through 4 years of age (prior to the fifth birthday). It is injected into the muscle in a 3-dose schedule and recommended to be administered at 2, 4, and 6 months of age. Currently, the CDC’s Advisory Committee on Immunization Practices has not made any recommendation regarding the use of VAXELIS. VAXELIS is expected to become available in the United States in 2020. 

The CDC recommends that all infants 4.4 lbs. and greater born to HBsAg-negative mothers be vaccinated with the first dose of hepatitis B vaccine within 24 hours of birth. Infants weighing less than 4.4 lbs. born to HBsAg-negative mothers should have the hepatitis B vaccine delayed until hospital discharge or one month of age. The final dose of hepatitis B vaccine should not be administered prior to 24 weeks of age. In populations with high rates of hepatitis B, vaccination with hepatitis B is recommended at birth, with the final dose recommended to be administered between 6 and 12 months of age.  Infants born to HBsAg-positive mothers are recommended to receive hepatitis B vaccine, along with hepatitis B immune globulin (HBIG) within 12 hours of birth. The CDC also recommends hepatitis B vaccination for adults with diabetes; household and sexual contacts of people with chronic hepatitis B infection; healthcare workers; people at increased risk for hepatitis B virus exposure due to occupational, behavioral, or medical factors; and international travelers to countries with high or intermediate hepatitis B infection rates. 

The hepatitis B Surface Antibody (anti-HBs) blood test can determine whether a person has immunity to Hepatitis B, however, this test is unable to differentiate between vaccine induced immunity or recovery from an acute infection.  

As of July 1, 2019, there had been 926 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following hepatitis B containing vaccinations, including 97 deaths and 829 serious injuries. 

Source: NVIC.ORG 

 

Hepatitis B Vaccine Adverse Reaction Articles

Numerous studies have been reported an association between hepatitis B vaccination and adverse reactions, such as neurologic, arthritic (rheumatoid arthritis), immunologic, and gastrointestinal. The consensus of some studies was that the adult female population, within close temporal association of hepatitis B vaccination, was more at increased risk for developing associated adverse reactions. 

Granel, B., P. Disdier, F. Devin, L. Swiader, J. M. Riss, L. Coupier, J. R. Harlé, J. Jouglard, and P. J. Weiller. "Occlusion of the central retinal vein after vaccination against viral hepatitis B with recombinant vaccines. 4 cases." Presse medicale (Paris, France: 1983) 26, no. 2 (1997): 62-65.

https://europepmc.org/article/med/9082411

 

Abstract 

Objectives

Hepatitis B vaccination has been proven to be effective and well-tolerated. Certain neurological, ocular, or systemic complications have, however, been reported to be induced by the vaccine. Clinicians should be aware of exceptional ocular complications.

Clinical report

Four patients under 50 years of age developed occlusion of the central vein of the retina after vaccination with recombinant hepatitis B vaccine. None of the classical causes of occlusion of the central vein of the retina could be evidenced.

Discussion

Several pathophysiological hypotheses have been proposed to explain these ocular manifestations after vaccination: role of immunocomplexes, antigenic cross-reactions, role of immediate hypersensitivity, simulation of a pathogenic lymphocyte repertoire. None of these hypotheses is entirely satisfactory. It is important however to emphasize the need for a complete general evaluation, including an ophthalmological examination in the presence of unexplained ocular manifestations following hepatitis B vaccination.

 

Guiserix, José. "Systemic lupus erythematosus following hepatitis B vaccine." Nephron 74, no. 2 (1996): 441-441

 

Highlights

A 26-vear-old mixed-blood social worker woman was given a first recombinant antihepatitis vaccine dose (GenHevac-B) in September 1994. One week later, she experienced fever and chills, then a vaginal discharge. followed by cutaneous eruption of the face, arms, and legs. She was referred to the local hospital where ocular and pulmonary' involvements were noticed. Cutaneous biopsy showed lupus-like histopathologic changes, but immunofluorescence was negative, as antinuclear antibody testing. In November. the diagnosis was assessed by antinuclear antibodies at 1/500 homogeneous, Farr test 92 1U, complement component C3 246 (normal range 550-1.200) and C4 level 58 (200-500) mg/1. Like Tudela et al., we believe that vaccination can induce an immune stimulation that may reveal or trigger a latent auto-immune genetic predisposition. The mechanism seems different from the chemical or drug-induced lupus-like syndrome. and closer to classical SLE. Whether thimerosal used as preservative, or aluminium hydroxide used as adjuvant, or Hb surface antigen protein [8] as in polyarteritis nodosa is the cause of the syndrome [2], LED should now be added to the list of rare recombinant hepatitis B vaccine side-effects. When any immune lupus-like manifestation occurs, the patient should be checked up on systematically about a recent antihepatitis B vaccination, and the protocol be stopped, antinuclear antibody testing should be performed 3 months later. An early short corticosteroid course may be relevant.

 

Herroelen, L., J. De Keyser, and G. Ebinger. "Central-nervous-system demyelination after immunisation with recombinant hepatitis B vaccine." The Lancet 338, no. 8776 (1991): 1174-1175.

 

Abstract

2 patients had neurological symptoms and signs, with evidence of central-nervous-system demyelination, 6 weeks after administration of recombinant hepatitis B vaccine. 1 had known multiple sclerosis but the other had no history of neurological disease; both had HLA haplotypes DR2 and B7, which are associated with multiple sclerosis. A causal link between vaccination and demyelination cannot be established from these 2 case-reports, but the time interval would fit a proposed immunological mechanism.

 

Maillefert, J. F., J. Sibilia, E. Toussirot, E. Vignon, J. P. Eschard, B. Lorcerie, R. Juvin et al. "Rheumatic disorders developed after hepatitis B vaccination." Rheumatology 38, no. 10 (1999): 978-983.

 

Abstract

Objective. To obtain an overview of rheumatic disorders occurring after hepatitis B vaccination.

Methods. A questionnaire was sent to rheumatology departments in nine French hospitals. Criteria for entry were rheumatic complaints of 1 week's duration or more, occurrence during the 2 months following hepatitis B vaccination, no previously diagnosed rheumatic disease and no other explanation for the complaints.

Results. Twenty-two patients were included. The observed disorders were as follows: rheumatoid arthritis for six patients; exacerbation of a previously non-diagnosed systemic lupus erythematosus for two; post-vaccinal arthritis for five; polyarthralgia–myalgia for four; suspected or biopsy-proved vasculitis for three; miscellaneous for two.

Conclusions. Hepatitis B vaccine might be followed by various rheumatic conditions and might trigger the onset of underlying inflammatory or autoimmune rheumatic diseases. However, a causal relationship between hepatitis B vaccination and the observed rheumatic manifestations cannot be easily established. Further epidemiological studies are needed to establish whether hepatitis B vaccination is associated or not with an incidence of rheumatic disorders higher than normal.

 

Pope, J. E., A. Stevens, W. Howson, and D. A. Bell. "The development of rheumatoid arthritis after recombinant hepatitis B vaccination." The Journal of rheumatology 25, no. 9 (1998): 1687-1693.

Abstract 

Objective

Hepatitis B vaccination has been associated with reactive arthritis and rarely rheumatoid arthritis (RA). We defined the clinical, serologic, and immunogenetic background of patients developing RA, soon after recombinant hepatitis B vaccination.

Methods

The clinical, serologic, and HLA antigens of a cluster of firefighters who developed arthritis after prophylactic recombinant hepatitis B vaccination (5 subjects), as well as a second group of sporadic cases of arthritis (6 patients) after hepatitis B vaccination are described.

Results

Ten of 11 patients fulfilled revised American College of Rheumatology criteria for RA. All cases had persistent arthritis for more than 6 months; at 48 months followup 2 cases no longer had inflammatory arthritis. Nine patients required disease modifying antirheumatic drugs. Five subjects were HLA-DR4 positive. HLA class II genes expressing the RA shared motif were identified in 9/11 patients genotyped for HLA-DRbeta1 and DQbeta1 alleles (0401, 0101, or 0404). All the firefighters shared the HLA-DRbeta1 allele 0301 and the DQbeta1 allele 0201, with which it is in linkage disequilibrium.

Conclusion

These polymorphic residues in the binding site of the MHC class II molecules of the affected patients appear capable of binding some peptide sequences of the recombinant vaccine peptides they received and may be responsible for hepatitis B vaccine triggering development of RA in these cases. Recombinant hepatitis B vaccine may trigger the development of RA in MHC class II genetically susceptible individuals.

 

Ronchi, F., P. Cecchi, F. Falcioni, A. Marsciani, G. Minak, G. Muratori, P. L. Tazzari, and S. Beverini. "Thrombocytopenic purpura as adverse reaction to recombinant hepatitis B vaccine." Archives of disease in childhood 78, no. 3 (1998): 273-274.

 

Abstract 

Three cases of immune thrombocytopenic purpura after the first dose of recombinant hepatitis B vaccine occurred in infants under 6 months of age. Other possible causes of this condition were excluded. Antiplatelet antibodies were present. A defect in platelet production was excluded in two children. Corticosteroid treatment was eVective. Subsequent administration of other vaccines (against polio, diphtheria, and tetanus) did not cause relapse of thrombocytopenia.

 

Tourbah, A., O. Gout, R. Liblau, O. Lyon-Caen, C. Bougniot, M. T. Iba-Zizen, and E. A. Cabanis. "Encephalitis after hepatitis B vaccination: recurrent disseminated encephalitis or MS?." Neurology 53, no. 2 (1999): 396-396.


Objective: To describe clinical and MRI features of patients with a disease suggestive of CNS inflammation after hepatitis B vaccination.

Methods: Eight patients with confirmed CNS inflammation occurring less than 10 weeks after hepatitis B vaccination are described. They received follow-up clinically and on MRI for a mean period of 18 months.

Results: Clinical and MRI findings were compatible with acute disseminated encephalomyelitis. However, clinical follow-up, repeated MRI, or both showed the persistence of inflammatory activity, which makes this encephalitis more suggestive of MS than of acute disseminated encephalomyelitis.

Conclusion: The persistent inflammatory activity observed clinically and on MRI in these patients is comparable with that usually observed in MS. Epidemiologic studies are currently testing the hypothesis of a triggering role of hepatitis B vaccination in CNS demyelination.

 

Tudela, Pere, Salvador Martí, and Jordi Bonal. "Systemic lupus erythematosus and vaccination against hepatitis B." Nephron 62, no. 2 (1992): 236-236.

 

Highlights

A 43-year-old woman, without a particularly relevant medical background, presented edema on both legs for 6 weeks. About 2 weeks before the onset of the symptoms, she had been administered a first dose of recombinant antihepatitis B vaccine (Engerix®-B). Laboratory data showed: hemoglobin 10 g/ dl, with a leukocyte and blood platelet count within a normal range; a certain deterioration of the renal function was observed, plasma creatinine 172 pmol/l, with proteinuria 1.8 g/24 h, and microscopic hematuria. Electrocardiogram and chest x-ray were normal. Haptoglobin and ferritin were within a normal range, and Coombs’ test resulted negative. Immunological study revealed an increase in IgG to 2,070 mg/dl (normal = 800-1,700) with IgM and IgA within normal limits. The dosage of the complement showed a decrease in C3 to 17 mg/dl (normal = 50-120), C4 to 4 mg/dl (normal = 20-50) and CHjo to 2 U/ml (normal = 75-125). Circulating immune complexes were 2 ug/ml (normal). The antinuclear antibodies were positive at 1/1,280 homogeneous pattern, and anti-DNA at 1/320, with positive anti-Ro and anti-La antibodies. The serologic test for syphilis and rheumatic serology was negative. A renal biopsy was practiced which showed a diffuse proliferative glomerulonephritis with extracapillary proliferation and positive immunofluorescence for different immunoglobulins and complement factors. With the diagnosis of lupus nephritis type IV. treatment was initiated with low doses of prednisone (0.5 mg/kg/day) and cyclophosphamide (500 mg/m:) in monthly boluses. The subsequent evolution was favorable; renal function went back to normal, the level of antinuclear antibodies and immune complexes decreased, and anti-DNA antibodies were negative again. The role of vaccination as an inducing factor in outbreaks of SLE has not been established up to now. Nevertheless, there are some facts that suggest that the administration of immunization to these patients may precipitate the clinical manifestations of the disease. Thus, the outbreak of lupus vulgaris after vaccination with BCG has been reported [3], On the other hand, in a study on the efficacy of vaccination against influenza in patients with SLE, the appearance of a certain deterioration of the renal affection was observed in 3 of the 202 patients studied [4], Perhaps, such immunization implies an increase in the number of immune complexes, which is an ill-tolerated phenomenon in these patients since they suffer from a decrease in their capacity of clearing such products. In another recent study on vaccination against hepatitis B in patients with renal failure, the lack of response to immunization was observed in those patients with SLE, which was attributed to the widely known dysfunction of B cells (5], In our case, the appearance of the clinical manifestations of the disease after immunization suggests that such immunization may have had a precipitating role in the autoimmune phenomena. The implication of this vaccine in such phenomena has not been reported to the moment.

Polio Vaccine Description and Reactions

 

Two different kinds of polio vaccines have been given to children in the U.S. since the 1950’s and 1960’s: a live attenuated oral polio vaccine (OPV), which is no longer used in the U.S.  but is given to children in other parts of the world; and an inactivated, injectable polio vaccine (IPV), which has been given to children in the U.S. since 2000. Inactivated polio vaccines contain poliovirus type 1, 2 and 3; however, the OPV currently in use is a bivalent vaccine containing only type1 and type 3 poliovirus. 

 

There are six inactivated, injectable polio vaccines licensed and marketed in the U.S. by pharmaceutical companies. Five of the polio containing vaccines are combination vaccines that include additional vaccines to prevent other viral or bacterial infections. The CDC recommends that infants and children receive a total of four doses of IPV with a dose at two and four months, between 6 and 18 months and between four and six years old.

 

Polio Vaccines Licensed for Use in the U.S.

Following is a list of currently available vaccines that contain the polio vaccine with links to the manufacturer product inserts (click on the name of the product):

  • IPOL, a polio vaccine containing inactive poliovirus (Monkey Kidney Cell) for individuals 6 weeks of age and older.

  • Pediarix, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, hepatitis B recombinant and inactivated poliovirus vaccines for children under 7 years of age. It is manufactured by GlaxoSmithKline.

  • Kinrix, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoids, acellular pertussis and inactivated poliovirus vaccines for children 4 to 6 years old. It is manufactured by GlaxoSmithKline.

  • Quadracel, a 4 in 1 combination vaccine containing diphtheria and tetanus toxoid, acellular pertussis and inactivated poliovirus vaccine for children 4 to 6 years old. It is manufactured by Sanofi Pasteur

  • Pentacel, a 5 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine for children under four years old. It is manufactured by Sanofi Pasteur Ltd.

  • VAXELIS, a 6 in 1 combination shot containing diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus b conjugate, and hepatitis B recombinant vaccine for children under 5 years of age. It is manufactured by MCM Vaccine Company. (Not currently available for use)

 

Source: NVIC.ORG 

Polio Vaccine Live Vs. Killed Virus History

The road to the Salk and Sabin polio vaccines has been one of tragedy as the first attempt at a killed polio vaccine ended in complete failure. In 1935, a young researcher at the New York University School of Medicine isolated a poliovirus strain and injected it into monkeys. He then ground up the spinal cords of the infected monkeys and put the tissues into formaldehyde, which was supposed to kill the virus. The researcher then inoculated monkeys, as well as hundreds of children, with the 'killed' virus. When some of the vaccinated monkeys were challenged with live poliovirus, however, they promptly died of the disease. Investigation then revealed that at least 1 child died and 3 others became paralyzed after receiving the 'killed' vaccine.

Source: Klein A. Trial by Fury. New York: Charles Scribner's Sons, 1972.

It was thought for some time that, since laboratory signs of poliovirus infection were found in the nervous system, the virus could only be grown in nerve tissue. After the 1935 disaster, scientists were afraid to use monkey nervous tissue to make a killed vaccine. Then it was discovered that the poliovirus could grow in monkey kidneys. This finding allowed Dr Jonas Salk to begin producing polio vaccines in 1952. Eventually, the laboratories making these vaccines would consume 200,000 monkeys a year.

Source: Smith J S. Patenting the Sun. New York: William Morrow and Company Inc., 1990.

As in 1935, formaldehyde was used by Salk to kill the polioviruses that he had isolated. Initial tests of his vaccine showed efficacy in preventing disease upon challenge of inoculated laboratory animals with live virus. The largest testing of a medical product in the history of man was then organized by the March of Dimes organization. The Salk vaccine trials were interrupted when it was discovered that vaccine lots produced by the Cutter Company had caused some monkeys and a total of 250 children and their contacts to develop complete or partial paralysis - 11 of the victims died.

 

Like Salk with his ‘killed’ vaccine, Dr Albert Sabin had to isolate viable virus from polio victims to develop his live oral polio vaccine. The virus strains had to be potent enough to elicit antibodies when ingested, but not so strong as to return to virulence after undergoing Pasteur's method of repeatedly infecting laboratory animals and harvesting the weakened viruses. Sabin also grew his viruses in monkey kidney tissues, but unlike Salk, he did not treat the viruses with formaldehyde.

Beginning in 1956, Sabin's live polio vaccine was tested in the Soviet Union and Eastern Europe by the administration of sweet syrup and sugar cubes to over 77,000,000 people. The live oral vaccine was then adopted as the polio vaccine of choice for the United States and most of the world.

Polio Vaccine History and Simian Virus 40 (SV40)

In 1960 that an NIH scientist named Bernice Eddy discovered that rhesus monkey kidney cells used to make the Salk polio vaccine and experimental oral polio vaccines could cause cancer when injected into lab animals. Later that year the cancer-causing virus in the rhesus monkey kidney cells was identified as SV40 or simian virus 40, the 40th monkey virus to be discovered. The public was not told the truth about this in 1960. The SV40 contaminated stocks of Salk polio vaccine were never withdrawn from the market but continued to be given to American and Russian children until early 1963 with full knowledge of federal health agencies.  Between 1955 and early 1963, nearly 100 million American children had been given polio vaccine contaminated with the monkey virus, SV40. 

The Director of the Division of Biologics Standards of the NIH issued a memorandum to manufacturers of the live oral polio vaccine on June 30, 1961, ordering them to exclude SV40-contaminated lots from all vaccines used in the United States. Since the Asian monkeys used in vaccine production were up to l00% infected with SV40, the manufacturers began to import large quantities of African green monkeys which did not naturally harbor the virus or show antibodies to it upon capture in the wild. Thus, vaccine production switched from predominantly Asian monkeys to African green monkeys in 1961.

Tumors caused by SV40 in animals were often sarcomas occurring at the site of vaccination but were also found in kidneys and lungs. 3-week-old hamsters infected with SV40 produced a wide variety of tumors, most of which were lymphomas and bone cancers. SV40 was also discovered to transform human cells in vitro, and the transformed cells could then produce localized tumors when injected back into the human donors.

Source: Shah, Keerti, and Neal Nathanson. "Human exposure to SV40: review and comment." American journal of epidemiology 103, no. 1 (1976): 1-12.

Initially, there was no definite evidence that SV40 was active in humans. Even as late as 1975, the journal Science wrote: Who could have argued against the benefits of polio vaccine in the 1950s -- yet the vaccine received by millions of people in the United States and abroad is now known to have been contaminated with SV40, a monkey virus which causes tumors in hamsters, though not, as luck would seem to have it, in man.

Source:  Anon. News and Comment. Genetics: Conference sets strict controls to replace moratonum. Science 1975; 187: 931-935.

However, by then SV40 had been isolated from the brains of 2 patients with progressive multifocal leukoencephalopathy (PML)  and from an advanced melanoma. 

Sources: 

Weiner L P, Herndon R M, Narayan O et al. Isolation of virus related to SV40 from patients with progressive multifocal leukoencephalopathy. New Engl J Med 1972; 286: 385-390.

Soriano F, Shelburne C E, Gökcen M. Simian virus 40 in a human cancer. Nature 1974; 249: 421-424.

Moreover, an Australian study demonstrated a correlation between polio immunization and the development of cancers in children over 1 year of age. 

Source: Innis M D. Oncogenesis and poliomyelitis vaccine. Nature 1968; 219: 972-973.

In other reports, footprints of SV40 were found in adult and pediatric brain tumors and an increased occurrence of intracranial tumors was noted among persons who had received the contaminated vaccines.

Sources: 

Geissler E (SV40 in human intracranial tumors: Passenger virus or oncogenic 'hit-and-run' agent') Z Klin Med 1986; 41: 493-495.

Bergsagel D J, Finegold M J, Butel J S et al. DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N Engl J Med 1992: 326: 988-993.

Geissler E. SV40 and human brain tumors Prog Med Virol 1990; 37: 211-222.

 SV40 was also implicated in the development of bladder, oromaxillofacial, and parotid gland tumors. 

Sources:

Bravo M P, Del Rey-Calero J. Association between the occurrence of antibodies to simian vacuolating virus 40 and bladder cancer in male smokers. Neoplasma 1988; 35: 285-288.

Stoian M, Suru M, Zaharia O et al. (Possible relation between viruses and oromaxillofacial tumors. II. Research on the presence of the SV40 antigen and specific antibodies in patients with oromaxillofacial tumours). Virologie 1987; 38: 35-40.

Stoian M, Zaharia O, Suru M et al. (Possible relation between viruses and oromaxillofacial tumors. II. Detection of SV40 antigen and of anti-SV40 antibodies in patients with parotid gland tumors). Virologie 1987; 38: 41-46.

It has been discovered that endothelial cells transformed by SV40 cause Kaposi sarcoma-like tumors in immunodeficient mice.

Source: O'Connell K, Landman G, Farmer E et al. Endothelial cells transformed by SV40 T-antigen cause Kaposi's sarcoma-like tumors in nude mice. Am J Pathol 1991; 139(4): 743-749.

Research shows that latent SV40 infection can be reactivated by simian immunodeficiency virus (SIV) to cause kidney cancers and PML in monkeys. 

Horvath C J, Simon M A, Bergsagel D J et al. Simian virus 40-induced disease in rhesus monkeys with simian acquired immunodeficiency syndrome. Am J Pathol 1992; 140: 1431-1440.

Yet despite these findings, no major studies of the possible consequences of the massive population exposure to SV40 have been conducted to date.

In 1988, a study conducted between 1959 and 1965 in 58 807 pregnant women was reviewed. 

Source: Rosa F W, Sever J L, Madden D L. Absence of antibody response to simian virus 40 after inoculation with killed-poliovirus vaccine of mothers of offspring with neurologic tumors. N Engl J Med 1988; 318: 1469.

Data from this Collaborative Perinatal Project demonstrated that the risk of brain tumors among offspring of mothers who had received the Salk vaccine was 13 times the risk among offspring of mothers who had not. The stored serum samples of the mothers of offspring with cancers were tested for antibodies to SV40. Despite the association between the vaccine and the occurrence of brain tumors in vaccinee offspring, none of the mothers' sera were positive. The conclusion of the reviewers was that the cancers were probably caused by a ‘still-unidentified infection originating in the polio vaccine;’ which (according to the reviewers) was known to have been contaminated with numerous simian viruses.

Source: Rosa F W, Sever J L. Madden D L. Response to: Neurologic tumors in offspring after inoculation of mothers with killed-poliovirus vaccine. N Engl J Med 1988; 319: 1226.

Today, U.S. federal health agencies admit the following two facts: 

  1. Salk polio vaccine released for public use between 1955 and 1963 was contaminated with SV40.

  2. SV40 has been proven to cause cancer in animals. 

There are scientists associated with the US government who continue to deny that SV40 causes human cancer or that SV40 associated cancers have had any effect on cancer rates since the early 1960’s. However, highly credentialed non-government scientists in multiple labs around the world continue to identify SV40 in human brain and lung cancers of children and adults and are finding that SV40 is also associated with bone cancers and Non-Hodgkin’s Lymphomas. Most of these independent scientists have concluded that SV40 does cause human cancers. 

Gazdar AE, Butel JS, Carbone M. 2002. SV40 and human tumours: myth, association or causality? Nature 2: 957-964) 

Articles of SM 40 Polio Vaccine

Butel, Janet S., and John A. Lednicky. "Cell and molecular biology of simian virus 40: implications for human infections and disease." Journal of the National Cancer Institute 91, no. 2 (1999): 119-134.

 

Abstract

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

 

Carbone, Michele, Paola Rizzo, and Harvey I. Pass. "Simian virus 40, polio vaccine and human tumors: a review of recent developments." Oncogene 15, no. 16 (1997): 1877-1888.

 

Recently, wild-type SV40 and/or DNA sequences indistinguishable from SV40 have been detected in specific types of human tumors: ependymoma and choroid plexus tumors, mesothelioma, osteosarcoma and sarcoma. The same tumor types will develop in hamsters after injection with SV40. These findings are interesting in themselves for they could shed light on the pathogenesis of these tumors. These findings also have public health implications. SV40 was found to have contaminated the polio vaccine and the adenovaccines from 1955 until 1963, therefore resulting in the inadvertent injection of millions of people with this tumor virus. Moreover, our society pays a high cost for asbestos causality, a carcinogen associated with the development of mesothelioma. In addition to asbestos, the potential impact of finding another possible cause for mesothelioma (i.e., SV40), as well as the possible pathogenic role of the contaminated polio vaccines, has generated considerable public interest and concern. To discuss these recent findings, the NIH (National Institutes of Health) and the FDA (Food and Drug Administration), organized an International Conference at the NIH, Bethesda, MD, January 27 ± 28, 1997. The association of SV40 with human mesothelioma was also discussed in a special session at the IV International Mesothelioma Conference that was held at the University of Pennsylvania, Philadelphia, PA, May 13 ± 16, 1997. The purpose of this review is to summarize data, from the discovery of the contaminated polio vaccine to the most recent findings presented at the meetings in Bethesda and Philadelphia, to discuss technical and other problems associated with this research, and the potential for using these findings to develop new diagnostic and therapeutic approaches for SV40- associated malignancies.

Carroll-Pankhurst, C., E. A. Engels, H. D. Strickler, J. J. Goedert, J. Wagner, and E. A. Mortimer Jr. "Thirty-five-year mortality following receipt of SV40-contaminated polio vaccine during the neonatal period." British journal of cancer 85, no. 9 (2001): 1295-1297.

 

Cutrone, Rochelle, John Lednicky, Glynis Dunn, Paola Rizzo, Maurizio Bocchetta, Konstantin Chumakov, Philip Minor, and Michele Carbone. "Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961." Cancer research 65, no. 22 (2005): 10273-10279.

 

Abstract 

Some polio vaccines prepared from 1954 to 1961 were contaminated with infectious SV40. It has been assumed that all polio vaccines were SV40 free in the United States after 1961 and in other countries after 1962. Following a WHO requirement that was prompted by the detection of SV40 in some human tumors, we conducted a multilaboratory study to test for SV40 polio vaccines prepared after 1961. Vaccine samples from 13 countries and the WHO seed were initially tested by PCR. The possible presence of intact and/or infectious SV40 DNA in PCR-positive samples was tested by transfection and infection of permissive CV-1 cells. All results were verified by immunohistochemistry, cloning, and sequencing. All the vaccines were SV40 free, except for vaccines from a major eastern European manufacturer that contained infectious SV40. We determined that the procedure used by this manufacturer to inactivate SV40 in oral poliovirus vaccine seed stocks based on heat inactivation in the presence of MgCl2 did not completely inactivate SV40. These SV40- contaminated vaccines were produced from early 1960s to about 1978 and were used throughout the world. Our findings underscore the potential risks of using primary monkey cells for preparing poliovirus vaccines, because of the possible contamination with SV40 or other monkey viruses and emphasize the importance of using well-characterized cell substrates that are free from adventitious agents. Moreover, our results indicate possible geographic differences in SV40 exposure and offer a possible explanation for the different percentage of SV40-positive tumors detected in some laboratories. (Cancer Res 2005; 65(22): 10273-9)

 

Kops, Stanley P. "Oral polio vaccine and human cancer: a reassessment of SV40 as a contaminant based upon legal documents." Anticancer research 20, no. 6C (2000): 4745-4749.

Abstract

To date, the scientific literature and research examining SV40 and cancer-related diseases has been based upon an assumption that SV40 was not present in any poliovirus vaccine administered in the United States and was removed from the killed polio vaccine by 1963. The basis for this presumption has been that the regulations for live oral polio vaccine required that SV40 be removed from the seeds and monovalent pools ultimately produced in the manufacturing process. The Division of Biologic Standards permitted an additional two tissue culture passages--from three to five--in order to allow manufacturers the ability to remove this contaminant from the oral poliovirus vaccines then awaiting licensure. The confirmation of the removal by one drug manufacturer, Lederle, has been made public at an international symposium in January 1997, where its representatives stated that all of Lederle's seeds had been tested and screened to assure that it was free from SV40 virus. However, in litigation involving the Lederle oral polio vaccine, the manufacturer's internal documents failed to reveal such removal in all of the seeds. The absence of confirmatory testing of the seeds, as well as testimony of a Lederle manager, indicate that this claim of removal of SV40 and the testing for SV40 in all the seeds cannot be fully substantiated. These legal documents and testimony indicate that the scientific community should not be content with prior assumptions that SV40 could not have been in the oral polio vaccine. Only further investigation by outside scientific and independent researchers who can review the test results claimed in the January 1997 meeting and who can conduct their own independent evaluations by testing all the seeds and individual mono-valent pools will assure that SV40 has not been present in commercially sold oral poliovirus vaccine manufactured by Lederle.

Strickler, Howard D., Philip S. Rosenberg, Susan S. Devesa, Joan Hertel, Joseph F. Fraumeni Jr, and James J. Goedert. "Contamination of poliovirus vaccines with simian virus 40 (1955-1963) and subsequent cancer rates." Jama 279, no. 4 (1998): 292-295.

 

Abstract

Context Poliovirus vaccine contaminated with live simian virus 40 (SV40), a macaque polyomavirus that is tumorigenic in rodents, was used extensively in the United States between 1955 and 1963. Simian virus 40 DNA has recently been detected in several rare human tumors, including ependymomas, osteosarcomas, and mesotheliomas.

Objective To determine the risk of ependymoma, osteosarcoma, and mesothelioma among Americans who as children received SV40-contaminated poliovirus vaccine.

Design Retrospective cohort study using data from the Surveillance, Epidemiology, and End Results program (1973-1993) and the Connecticut Tumor Registry (1950-1969), as well as national mortality statistics (1947-1973).

Setting United States.

Participants Birth cohorts that were likely to have received SV40-contaminated poliovirus vaccine as infants, born 1956 through 1962 (60811730 person-years of observation); as children, born 1947 through 1952 (46430953 person-years); or that were unexposed, born 1964 through 1969 (44959979 person-years).

Main Outcome Measures Relative risk (RR) of each cancer among exposed compared with unexposed birth cohorts.

Results Age-specific cancer rates were generally low and were not significantly elevated in birth cohorts exposed to SV40-contaminated vaccine. Specifically, compared with the unexposed, the relative risk of ependymoma was not increased in the cohorts exposed as infants (RR, 1.06; 95% confidence interval [CI], 0.69-1.63), or as children (RR, 0.98; 95% CI, 0.57-1.69) nor did the exposed have an increased risk of all brain cancers. Osteosarcoma incidence also showed no relation to exposure as infants (RR, 0.87; 95% CI, 0.71-1.06) or children (RR, 0.85; 95% CI, 0.59-1.22). Last, mesotheliomas were not significantly associated with exposure, although the cohorts studied have not yet reached the age at which these tumors tend to occur.

Conclusions After more than 30 years of follow-up, exposure to SV40-contaminated poliovirus vaccine was not associated with significantly increased rates of ependymomas and other brain cancers, osteosarcomas, or mesotheliomas in the United States.
 

Strickler, H. D., J. J. Goedert, M. Fleming, W. D. Travis, A. E. Williams, C. S. Rabkin, R. W. Daniel, and K. V. Shah. "Simian virus 40 and pleural mesothelioma in humans." Cancer Epidemiology and Prevention Biomarkers 5, no. 6 (1996): 473-475.

 

Abstract It has been reported that DNA of 5V40, a virus of Asian macaques that is tumorigenic for rodents and can transform human cells in vitro, is present in pleural mesotheliomas and in several other cancers. To verify these observations, we tested paraffin sections from mesothelioma tissues of 50 patients for SV4O DNA using PCR with two separate sets of primers. The analytic sensitivity for detection of 5V40 DNA was 1-10 genome copies. We also tested the specimens for 3-globin by PCR to assess the suitability of the specimen DNAs for amplification. -Gbobin amplification was detected in 48 of the 50 specimens, but SV4O DNA was not detected in any tumors, with either of two 5V40 primer sets. Furthermore, sera from 34 additional patients with mesothelioma, 33 patients with osteosarcoma (another cancer reported to be SV4O-rebated) and 35 controls were tested for 5V40 antibodies by a plaque neutralization assay. The serological data, like the DNA results, did not support an association of SV4O with mesothelioma or with osteosarcoma; antibodies to SV4O were detected in three mesothelioma patients, in one osteosarcoma patient, and in one control. These findings call into question the association of SV4O with mesothelioma. Introduction SV4O infects Asian macaques in nature. Experimentally, it can induce tumors in rodents (1, 2) and can immortalize or transform many different cell types in vitro, including cells of human origin (3, 4). The possibility that SV4O may be associated with human cancers has been investigated several times in the past, with equivocal results (5-10). Recently, DNA of SV4O or an “SV4O-like” virus has been detected in human cancers using PCR (11, 12). Pleural mesotheliomas in adults (1 1) and ependymomas and choroid plexus tumors in children (12) were shown by PCR to contain SV4O DNA sequences in a barge Received 1/3/96; revised 3/10/96; accepted 3/12/96. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. I To whom requests for reprints should be addressed, at Department of Health and Human Services, Public Health Service, National Cancer Institute, NIH, EPN 434, Bethesda MD 20892. percentage of cases. In addition, a number of the tumor specimens tested were also shown by immunochemistry to contain SV4O large T antigen (1 1, 12). In a subsequent PCR study, SV4O DNA was reported to be present in osteosarcomas, osteoblastomas, chondrosarcomas, giant cell tumors, Ewing’s sarcomas, liposarcomas, and Li-Fraumeni cell lines (13). The public health implications of a relationship between 5V40 and human cancers could be substantial. More than one hundred million people worldwide were exposed to SV4O during the late 1950s and early 1960s, because polio and adenovirus vaccines, which were grown in monkey-kidney cell cultures, were inadvertently contaminated with 5V40 (14). Formalin-inactivated as well as live-attenuated vaccines contained infectious 5V40 (14). Despite occasional reports of 5V40 in human cancer (5, 6), epidemiological and virological studies have failed to demonstrate any increases in cancers associated with vaccine related SV4O exposure (7-10, 14). Furthermore, vaccines manufactured after 196 1 were required to be free of SV4O contamination (15). Therefore, the finding of SV4O in cancers of individuals who could not have received SV4O-contaminated vaccines (e.g., those born after 1961), implies not only that human infection with SV4O continues to occur, but that, in the case of children with ependymomas and choroid plexus papilloma, the infection is transmitted from infected mothers to their offspring. We examined human pleural mesotheliomas for the presence of SV4O DNA sequences and analyzed sera from mesothelioma and osteosarcoma patients for antibody evidence of infection with SV4O.

 

Testa, Joseph R., Michele Carbone, Ari Hirvonen, Kamel Khalili, Barbara Krynska, Kaija Linnainmaa, Frederick D. Pooley, Paola Rizzo, Valerie Rusch, and Guang-Hui Xiao. "A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas." Cancer research 58, no. 20 (1998): 4505-4509.
 

Abstract

Exposure to the carcinogen asbestos is a major factor in the develop ment of malignant mesothelioma. However, not all mesotheliomas are associated with asbestos exposure, and only a small minority of people exposed to asbestos develop mesothelioma. Therefore, the identification of the cofactors that render certain individuals more susceptible to asbestos or that cause mesothelioma in people not exposed to asbestos has been a major priority of the International Mesothelioma Interest Group. The possible association of SV40 with mesothelioma was recently discussed in a special session at the Fourth International Mesothelioma Interest Group Conference, and it was decided to conduct a multi-institutional study to independently verify the presence of this tumor virus in mesotheliomas. We report the results of this investigation: (a) DNA and protein analyses revealed SV40 sequences and SV40 large T antigen expression in 10 of 12 mesotheliomas tested (83%); and (/') electron microscopy demonstrated variable amounts of asbestos fibers in 5 (71%) of 7 corresponding lung tissues available for analysis. Our results demonstrate that SV40 DNA is frequently present and expressed in mesotheliomas in the United States. Because our data demonstrate that some patients test positive for both SV40 and asbestos, the possibility that these two carcinogens interact should be investigated in future studies.

Shingles Vaccine Description and Reactions

There are two shingles vaccines licensed for use in the U.S.: Zostavax live attenuated vaccine by Merck and Shingrix recombinant vaccine by GlaxoSmithKline Biologicals.

Zostavax live attenuated shingles vaccine licensed in 2006 is a much more potent version of Varivax chickenpox vaccine containing 19,500 plaque forming units of Oka/Merck varicella zoster virus versus 1,350 plaque forming units in the chickenpox vaccine.1 Administration of this preservative free vaccine is a subcutaneous (under the skin) in a .65mL single dose series containing sucrose, hydrolyzed porcine (pig) gelatin, urea (urine component), sodium chloride, monosodium L-glutamate, sodium phosphate dibasic, potassium phosphate monobasic, potassium chloride, MRC-5 cells (1966 aborted human male lung tissue)2, neomycin and bovine (cow) calf serum (blood plasma).3 More information can be found in the manufacturer’s product insert maintained on the U.S. Food and Drug Administration’s (FDA) website.

Shingrix adjuvanted recombinant vaccine licensed in 2017 is a two-dose series vaccine administered intramuscularly (injected into muscle) and is a genetically engineered vaccine. Each preservative free .5mL dose contains sucrose, sodium chloride, dioleoyl phosphatidylcholine (DOPC), potassium dihydrogen phosphate, cholesterol, sodium dihydrogen phosphate dihydrate, disodium phosphate anhydrous, dipotassium phosphate, polysorbate 80, Chinese Hamster Ovary (CHO) cell proteins, and DNA. This vaccine is an adjuvanted vaccine using AS01, which is a squalene (shark oil) based adjuvant. More information can be found in the manufacturer’s product insert maintained on the U.S. Food and Drug Administration’s (FDA) website.

Source: NVIC.ORG 

Varicella (Chickenpox) Vaccines Description and Reactions


There are currently two varicella (chickenpox) vaccines used in the United States: 

1) Varivax, a live chickenpox virus vaccine and 

2) ProQuad, a combination measles-mumps-rubella-varicella (MMRV) live virus vaccine, both produced and distributed by Merck.

 

The CDC recommends children receive a first dose of chickenpox vaccine between age 12 and 15 months, and a second dose between age 4 and 6. Mild side effects, such as redness, rash, or pain at the injection site, as well as fever, have been reported following chickenpox vaccination. More serious side effects of chickenpox vaccine include meningitis, pneumonia, seizures, full body rash, allergic reaction, and death. Mild side effects following MMRV vaccination include rash, redness, or pain at the injection site, fever and swelling of the glands in the neck or cheeks. More serious side effects of MMRV vaccine may include loss of hearing, meningitis, pneumonia, full body rash, seizure, coma, brain damage, severe allergic reaction, and death. 

 

Chickenpox vaccine is reported to be between 70 and 90 percent effective at preventing chickenpox and between 90 and 100 percent effective at preventing moderate to severe illness from chickenpox infection. The widespread use of chickenpox vaccine in the U.S. has substantially increased the rate of shingles infections in adults, as a natural boost of immunity from exposure to chickenpox in the environment is no longer occurring. 

 

As of Aug 1, 2020, there have been more than 173 claims filed in the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following chickenpox vaccination, including 11 deaths and 162 serious injuries.

 

Using the MedAlerts search engine, as of June 30, 2020, there have been more than 92,965 reports of chickenpox vaccine reactions, hospitalizations, injuries, and deaths following chickenpox vaccinations made to the federal Vaccine Adverse Events Reporting System (VAERS); this includes 210 related deaths, 3,368 hospitalizations, and 782 related disabilities. Over 69 percent of varicella vaccine-related adverse events occurred in children six years old and under.

Source: NVIC.ORG