posted with permission
Vinu Arumugham responds to the authors of Food allergen component proteins are not detected in early-childhood vaccines published in The Journal of Allergy and Clinical Immunology: In Practice
|Date:||Wed, 30 Jan 2019 01:06:58 -0800|
|To:||firstname.lastname@example.org , email@example.com|
This is regarding your study – Food allergen component proteins are not detected in early-childhood vaccines. (1)
Thank you for performing this study. I recall requesting Dr.Platts-Mills that the Prevnar 13 vaccine be tested for peanut protein. I am happy to see that was performed as well. While the data is important, there are many serious issues with your conclusions and interpretation.
Fact 1: Vaccines contain food proteins. There are no controls for labeling or limiting cross contamination among vaccines and other medical products. Vaccine and excipient makers use numerous food products during manufacture and could also be using shared equipment which can be a source of contamination. The US National Academy of Medicine has concluded and warned that vaccines include numerous food proteins including peanut, sesame, soy, milk, gelatin, egg, beef, fish etc. (2)
“Allergens in Vaccines, Medications, and Dietary Supplements
Physicians and patients with food allergy must consider potential food allergen exposures in vaccines, medications, and dietary supplement prod- ucts (e.g., vitamins, probiotics), which are not regulated by labelling laws. Also, excipients (i.e., substances added to medications to improve various characteristics) may be food or derived from foods (Kelso, 2014). These include milk proteins; soy derivatives; oils from sesame, peanut, fish or soy; and beef or fish gelatin. The medications involved include vaccines; anesthetics; and oral, topical, and injected medications. With perhaps the exception of gelatin, reactions appear to be rare overall, likely because little residual protein is included in the final preparation of these items. The specific risk for each medication is not known.
Vaccines also may contain food allergens, such as egg protein or gelatin.”
Many food proteins in vaccines have both been declared and measured. For example, milk proteins (3), gelatin (4,5) and egg proteins (6).
Fact 2: Food proteins in vaccines cause the development of food allergies. The US Institute of Medicine studied the entire vaccine literature from 1950 to 2011 to come to this conclusion. (7)
p. 65 (pdf p. 94):
“Adverse events on our list thought to be due to IgE-mediated hypersensitivity reactions
Antigens in the vaccines that the committee is charged with reviewing do not typically elicit an immediate hypersensitivity reaction (e.g., hepatitis B surface antigen, toxoids, gelatin, ovalbumin, casamino acids). However, as will be discussed in subsequent chapters, the above-mentioned antigens do occasionally induce IgE-mediated sensitization in some individuals and subsequent hypersensitivity reactions, including anaphylaxis.”
Here are examples of vaccine and injection induced IgE mediated sensitization that the IOM used to come to its conclusion.
Egg protein containing vaccines induce IgE mediated sensitization to egg proteins. (8,9)
Similarly, gelatin (4,5), influenza viral proteins (10–13), toxoids (14–16), Hepatitis B virus surface antigen (17).
Repeated bee stings cause IgE mediated allergy to bee venom. (18)
Bovine serum albumin (BSA) containing vaccines caused IgE mediated sensitization to BSA in horses. (19)
Similar results in dogs. (20–22)
Your team’s own study (23,24) confirmed the above. So food protein containing vaccines causing the development of food allergies is NOT a hypothesis, it is a fact. (25,26)
When designing a new product, we first build only a few prototypes. If the prototypes fail, you know you have a major design problem. Your team’s WAO study with n=2 was exactly like that. A two out of two failure (allergy boost), is a very valuable outcome showing fundamental design problems with the vaccines.
You make these assertions below but did not provide a reason or cite any references.
“The likelihood is low that early-childhood vaccines would contain food allergens.”
There are no specifications or controls. (25) Vaccine and excipient makers use numerous food products during production. So what is the basis for this statement?
“These findings do not support the concept that early-childhood vaccines or VitK injections contain allergy-causing food allergens.”
It is impossible to make such a sweeping claim unless you are able to detect the presence of even one molecule of the allergen.
“Without evidence of significant food allergen within the vaccines, the aforementioned hypothesis of vaccine-associated sensitization is unsupported.”
“Although the ELISA detection limits are quite low, the amount of allergen required to cause sensitization is poorly understood.”
As you admit, the amount of allergen required for sensitization is unknown. So how do you know how much is “significant food allergen”? With your limited detection capability, it is therefore impossible to jump to the conclusion that “the aforementioned hypothesis of vaccine-associated sensitization is unsupported.”, especially after you yourself have demonstrated that these food protein containing vaccines indeed boosted food allergies, exactly as expected from basic immunology. (23)
“Theoretically, it could be argued that the ELISA limits of detection may not be low enough, though this seems unlikely because these are the most sensitive assays available with detection limits in the nanogram range and have been used before to detect these antigens.”
What has the “most sensitive assays available” got to do with the amount of allergen required for human sensitization?
“What is reassuring is that children with peanut, cow’s milk, and egg allergy continue to receive these vaccines in the first year of life without having allergic reactions.”
That only allows you to make conclusions about the elicitation dose, not the sensitization dose.
Sensitization dose is less than elicitation dose (25). Kattan et al. showed that 8-18ng/ml of casein was enough to elicit anaphylaxis. That is proof that sensitization dose is much less than 8-18ng/ml for casein.
Also Norowitz et al. (12) found that ELISA was not as sensitive as “dot blot” technology for some of their work.
It looks at least for now, that the most sensitive allergen detector available is the human immune system. Your team’s own study (23) demonstrated that vaccines do indeed boost food allergies as would be expected with food allergen contaminated vaccines. It is rather strange that you have ignored that most important finding, based on this limited measurement data, while the dose needed for human sensitization (especially with the antigen adsorbed on a Th2 biased adjuvant), is still unknown.
Further, your measurement sample size is extremely small. As I describe (25), 7.4 mcg/ml of ovalbumin was detected in the influenza vaccine in 1967. But as much as 38 mcg/ml of ovalbumin was detected as recently as 2008. There is a huge variation among vendors, between years from the same vendor and among lots.
Unlike your WAO study situation, here you are trying to prove the safety of vaccines. Continuing the prototype example, when we go into volume production we have to build large number of products and test them to ensure quality. Likewise, to prove vaccine safety with regards to food protein contamination, such a small sample size is obviously inadequate to assess the quality of tens of millions of vaccine doses. Arepanrix and Pandemrix vaccines manufactured by the same company – GSK, in two different countries, had different levels of H1N1 nucleoproteins. Pandemrix induced narcolepsy (27) in thousands and Arepanrix did not. That’s another example of widely varying amounts of non-target proteins in vaccines and the callous disregard among vaccine makers for the devastating safety problems caused by off-target immune responses. (28,29)
I hope you will publish a correction addressing these serious issues because your conclusions are very misleading. Until you can establish food allergen sensitization amounts (taking into account the effects of aluminum adjuvant, numerous repeated vaccines, an atopic population that lacks helminth infections, c-section birth and antibiotic related sub optimal gut microbiome, etc.) and vaccine manufacturers put in place statistical quality controls that can detect and prevent such sensitization amounts, we can NEVER make the claim that vaccines do not cause sensitization. Alternately, vaccine production should not be based on food proteins at all. (3,5)
And, by the way, food proteins are not the only problem, aeroallergen contamination of vaccines results in asthma and numerous other diseases. (30)
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2. National Academies of Sciences and Medicine E. Finding a Path to Safety in Food Allergy: Assessment of the Global Burden, Causes, Prevention, Management, and Public Policy. Stallings VA, Oria MP, editors. Washington, DC: The National Academies Press; 2017.
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13. Davidsson A, Eriksson JC, Rudblad S, Brokstad KA. Influenza Specific Serum IgE is Present in Non-Allergic Subjects. Scand J Immunol. 2005 Dec;62(6):560–1.
14. Markt A, Björkstén B, Granström M. Immunoglobulin E responses to diphtheria and tetanus toxoids after booster with aluminium-adsorbed and fluid DT-vaccines. Vaccine. 1995;13(7):669–73.
15. Hedenskog S, Bjorksten B, Blennow M, Granstrom G, Granstrom M. Immunoglobulin E response to pertussis toxin in whooping cough and after immunization with a whole-cell and an acellular pertussis vaccine. Int Arch Allergy Appl Immunol. 1989;89(2-3):156–61.
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17. Smith-Norowitz TA, Tam E, Norowitz KB, Chotikanatis K, Weaver D, Durkin HG, et al. IgE anti Hepatitis B virus surface antigen antibodies detected in serum from inner city asthmatic and non asthmatic children. Hum Immunol. United States; 2014 Apr;75(4):378–82.
18. Eich-Wanger C, Muller UR. Bee sting allergy in beekeepers. Clin Exp Allergy. 1998;28(10):1292–8.
19. Gershwin LJ, Netherwood KA, Norris MS, Behrens NE, Shao MX. Equine IgE responses to non-viral vaccine components. Vaccine. Netherlands; 2012 Dec;30(52):7615–20.
20. Ohmori K, Masuda K, Maeda S, Kaburagi Y, Kurata K, Ohno K, et al. IgE reactivity to vaccine components in dogs that developed immediate-type allergic reactions after vaccination. Vet Immunol Immunopathol. 2005 Apr;104(3-4):249–56.
21. Tater KC, Jackson HA, Paps J, Hammerberg B. Effects of routine prophylactic vaccination or administration of aluminum adjuvant alone on allergen-specific serum IgE and IgG responses in allergic dogs. Am J Vet Res. 2005 Sep;66(9):1572–7.
22. HogenEsch H, Dunham AD, Scott-Moncrieff C, Glickman LT, DeBoer DJ. Effect of vaccination on serum concentrations of total and antigen-specific immunoglobulin E in dogs. Am J Vet Res. American Veterinary Medical Association; 2002 Apr 1;63(4):611–6.
23. Alice Hoyt, Peter Heymann, Alexander Schuyler, Scott Commins TAEP-M. Changes in IgE Levels Following One-Year Immunizations in Two Children with Food Allergy [Internet]. 2015. Available from: https://wao.confex.com/wao/2015symp/webprogram/Paper9336.html
24. Arumugham V. Vaccines and the development of food allergies: the latest evidence [Internet]. BMJ. 2016. Available from: https://www.bmj.com/content/355/bmj.i5225/rr-0
25. Arumugham V. Evidence that Food Proteins in Vaccines Cause the Development of Food Allergies and Its Implications for Vaccine Policy. J Dev Drugs. 2015;4(137):2.
26. Arumugham V. Professional Misconduct by NAM Committee on Food Allergy [Internet]. 2016. Available from: https://www.zenodo.org/record/1034559
27. Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2 (ABSTRACT ONLY). Sci Transl Med. 2015;7(294):294ra105–294ra105.
28. Arumugham V. Pandemrix and Arepanrix vaccine safety analysis and scrutiny fell short [Internet]. The BMJ. 2018. Available from: https://www.bmj.com/content/363/bmj.k4152/rr-14
29. Arumugham V. Pharmacovigilance is no substitute for good vaccine design [Internet]. The BMJ. 2018. Available from: https://www.bmj.com/content/362/bmj.k3948/rr-11
30. Arumugham V. Aeroallergen contamination of multi-dose and reconstituted vaccine vials cause the development of asthma, gastrointestinal diseases and proves vaccine makers and vaccine safety regulators are incompetent [Internet]. 2019 [cited 2019 Jan 22]. Available from: https://doi.org/10.5281/zenodo.2544037