Do food proteins in vaccines cause the development of food allergies?

Question

Vinu Arumugham writes in the article Evidence that Food Proteins in Vaccines Cause the Development of Food Allergies and Its Implications for Vaccine Policy published in the Journal of Developing Drugs:

Many studies since 1940 have demonstrated that food proteins in vaccines cause sensitization in humans. [...] It has been demonstrated that a smaller quantity of allergen is needed to cause sensitization than elicitation. [...] Nobel Laureate Charles Richet demonstrated over a hundred years ago that injecting proteins into humans or animals causes immune system sensitization to that protein. Subsequent exposure to the same protein can result in anaphylaxis. [...] 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.

Is there other peer-reviewed evidence that supports the thesis that allergens in modern vaccines cause the development of food allergies? Does the Institute of Medicine support this view?

Answer 1

Yes, the Institute of Medicine (now known as the Health and Medicine Division of the National Acadamies) stated in 2011 that food proteins in vaccines such as ovalbumin (chicken egg), casamino acids (cow's milk derived) do cause food allergies.

Adverse Effects of Vaccines: Evidence and Causality, 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.

For those who may not be familiar, here are the basics of allergy - a two step process:

Sensitization: When exposure to an allergen (food protein) occurs for the first time, there are no symptoms. Over a period of a few weeks, the immune system develops antibodies specific to the allergen. The person is now sensitized. In other words, the person has developed allergy to the specific food item. "IgE-mediated sensitization", is the technical description for development of allergy.

Elicitation: When a sensitized person is exposed to the same allergen again, they develop an immediate reaction (usually within minutes). Also called hypersensitivity reaction. This is called elicitation. A severe, life-threatening case of elicitation is known as anaphylaxis.

So in simple English, the IOM committee has concluded that food proteins such as gelatin, egg (ovalbumin) and milk (casamino acids are derived from milk) that are present in vaccines, cause healthy non-allergic people to develop allergies to those food items upon receiving the vaccine.

Further, they also reported in 2017 that there are numerous food proteins in vaccines and they are not regulated or labelled.

• Finding a Path to Safety in Food Allergy, p. 241

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."

In January 2017, the organisation was criticised for ignoring further evidence in an unpeer reviewed source by an unaffiliated individual, Vinu Arumugham: Professional Misconduct by NAM Committee on Food Allergy

Tetanus toxoids in the first dose of the tetanus vaccine caused sensitization (development of allergy to the toxoids). Allergic reactions were observed following the second dose of the vaccine. https://jamanetwork.com/journals/jama/article-abstract/1160278?redirect=true

The study thus revealed unexpectedly high rates of IgE responses to diphtheria and tetanus toxoids in a regular DT booster vaccination programme, which were associated to high rates of local side effects.

https://www.ncbi.nlm.nih.gov/pubmed/7668036

Repeated injection of egg containing vaccines produced egg allergy. http://www.nejm.org/doi/full/10.1056/NEJM195204032461403 https://www.cambridge.org/core/journals/epidemiology-and-infection/article/serological-examination-of-ige-and-iggspecific-antibodies-to-egg-protein-during-influenza-virus-immunization/A7329D0D9F0C3F383FD5989BBE77FBCB

Gelatin containing vaccines caused the development of gelatin allergy. https://www.pubfacts.com/detail/9949325/A-clinical-analysis-of-gelatin-allergy-and-determination-of-its-causal-relationship-to-the-previous-

https://www.ncbi.nlm.nih.gov/pubmed/14624794

An allergic (Th2) response to beta-lactoglobulin (a cow's milk protein) was observed following administration of vaccines containing cow's milk proteins. In other words, development of milk allergy was observed. https://www.ncbi.nlm.nih.gov/pubmed/17116347

Tetanus and pertussis vaccines contain cow's milk proteins because they are used as growth media. Once sensitized as above, the next cow's milk containing vaccine can cause an allergic reaction as described below: http://www.jacionline.org/article/S0091-6749(11)00747-0/fulltext

Anti-hepatitis B surface antigen IgE antibodies were observed following HepB vaccine administration. https://www.ncbi.nlm.nih.gov/pubmed/24374043

Basically, these illustrate that ANY protein injected can cause the development of allergy to that protein. The IOM listed all these proteins (antigens) as examples. This basic concept of injected proteins causing the development of allergy is of course more than a hundred years old and was described by Nobel Laureate Dr. Charles Richet.

https://www.nobelprize.org/nobel_prizes/medicine/laureates/1913/richet-lecture.html

Answer 2

Evidence:

1. Certain food-derived excipients contain food proteins either intentionally or unintentionally as contaminants.

Virtually all food allergens that generate IgE-mediated responses are proteins. In some cases the food excipients in medications are in fact proteins and thus capable of being allergenic. The amount and nature of (eg, how thoroughly hydrolyzed) these proteins might influence their allergenic potential. However, in many other cases the food excipient in the medication is a fat or carbohydrate and thus would not be expected to be allergenic. In these cases the excipient would have to be contaminated with protein for an allergen to be present. This type of contamination might well be random or variable. Source: Potential food allergens in medications

2. Components of vaccines have the potential to cause allergic reactions.

Vaccines, specifically individual components of the vaccine, are known to, although rarely, cause serious complications. Even after an allergic reaction after vaccination, it is difficult to ascertain whether the allergic reaction was caused by the vaccine itself or other factors. The vaccine components include active immunizing antigens, conjugating agents, preservatives, stabilizers, antimicrobial agents, adjuvants and culture media used in the preparation of the vaccine, as well as inadvertent contaminants that are introduced during vaccine handling. Almost all the vaccine components can be considered as potential triggers of an allergic reaction. Of particular importance are culture derived proteins from egg, gelatin and yeast. Other sources of allergic reaction are antibiotics and vaccination antigens. Source: Vaccine allergies

Rate of reported vaccine-induced adverse events are low and estimates of true allergic reactions to vaccines routinely used is not known.

The number of true allergic reactions to routine vaccines is not known; estimations range from 1 per 500000 to 1 per 1 000000 doses for most vaccines. Source: Vaccine hypersensitivity – update and overview

Life-threatening reactions such as death after routine vaccination are extremely rare.

According to Bohlke et al., reported cases of potential anaphylaxis after vaccination amount to 0.065 per 100000 given doses of vaccines. None of the episodes resulted in death. This underlines that life-threatening reactions after routine vaccination are exceptional events. Source: Vaccine hypersensitivity – update and overview

It is also true that egg and gelatin which are used as components of vaccines are potential allergens. However life threatening reactions are rare events.

When allergens such as gelatine or egg proteins are components of the formulation, the rate for serious allergic reactions may be higher. Nevertheless, anaphylactic, potentially life threatening reactions to vaccines are still a rare event (~1 per 1500000 doses). Source: Vaccine hypersensitivity – update and overview.

Vaccines rarely produce allergic reactions.

Vaccines rarely produce allergy or anaphylaxis (a rapid and serious form of allergic reaction). Overall, the total risk of anaphylaxis in children and adolescents after one vaccination has been reported as <1 case per one million doses. Source: Vaccine components

Milk and yeast which are used as substrate for growth of viral and bacterial components are also noted to be potential allergans.

Thus, no special precautions are required when administering vaccines to milk-allergic patients. However, should a milk allergic patient suffer an allergic reaction to one of these vaccines, the possibility of milk protein contaminating the vaccine should be considered. Source: International Consensus (ICON): allergic reactions to vaccines

Thus, both yeast allergy and adverse vaccine reactions attributable to yeast allergy appear to be exceedingly rare. A patient who reports yeast allergy should be carefully questioned about the nature of exposure and nature and timing of symptoms and undergo prick skin testing or serum specific IgE antibody testing with S. cerevisiae to reveal the rare patient who may have symptoms due to IgE-mediated yeast allergy. In such patients, it would seem prudent, prior to hepatitis B vaccination, to perform vaccine skin testing and, if positive, vaccine administration in graded doses as described above for gelatin containing vaccines or use a vaccine not grown in yeast. Source: International Consensus (ICON): allergic reactions to vaccines

3. International consensus on allergic reactions to vaccines is that pre-existing allergy in some cases is determined to be the cause of the allergic reactions to vaccines containing the component.

In some circumstances, pre-existing allergy to a vaccine component has been demonstrated to be the cause of anaphylactic reactions to vaccines containing the component (e.g. gelatin). However, allergy to components of vaccines has been suspected or demonstrated to be the cause of allergic reactions to vaccines only in very rare circumstances. Source: International Consensus (ICON): allergic reactions to vaccines

4. The 2012 report by the Institute of Medicine (IOM) now called the National Academy of Medicine (NAM) notes that the very rare hypersensitivity reactions caused by vaccine administration are more likely due to potential allergens among the vaccine constituents rather than the active ingredients of the vaccine but the actual mechanism directly causing the reaction is not known.

   However, the IOM concluded that there was no mechanistic evidence for an association between chronic urticaria and diphtheria, tetanus or pertussis vaccines. Source: Do Vaccines Cause Hypersensitivity Reactions?

5. Research shows that the true prevalence of food allergy is between 2% and 5% of the population of US and researchers feel that it is unnecessary advise to avoid certain immunizations in patients with true or assumed food allergies since risk of not vaccinating is a greater risk than that of vaccinating.

   Adverse food reactions have been reported in up to 25% of the US population at some point in their lives, with the highest prevalence observed during infancy and early childhood. Although reported adverse reactions to foods are common, true IgE-mediated food allergy represents only a small percentage of these reactions. Many studies indicate that the true prevalence of food allergy is between 2% and 5%. If someone is incorrectly diagnosed as having food allergy, unnecessary dietary restrictions may adversely affect his or her quality of life and nutritional status. Moreover, patients with true or assumed food allergies might unnecessarily be advised to avoid certain immunizations, which could have important adverse individual and population health consequences. Source : Food Allergies Are Rarely a Concern When Considering Vaccines for Adolescents

6. Regarding the claim in the article that "The Institute of Medicine (IOM) confirmed that food proteins in vaccines cause food allergy", it is very important to note that the NAM paper mentions that "the above-mentioned antigens do occasionally induce IgE-mediated sensitization in some individuals and subsequent hypersensitivity reactions, including anaphylaxis". The understanding should be that sensitization occurs in some individuals but not all and hence this claim cannot be generalized for the entire population as noted below from the NAM paper.

   Examples of allergen exposures thought to cause IgE-mediated anaphylaxis Many allergens have been associated with the development of IgE-mediated anaphylaxis. These include food (e.g., milk, egg, peanuts, tree nuts, shellfish, gelatin), food additives (e.g., some colorants, spices, yeast), venoms (e.g., insect stings), latex, and inhalants (e.g., animal danders and grass pollen) (Simons, 2010).

   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. Source: Adverse Effects of Vaccines: Evidence and Causality (2012) Chapter: 3 Evaluating Biological Mechanisms of Adverse Events

Summary:

1. TL;DR: There are several non-modifiable and modifiable factors which play a role in the development of food allergies which is further explained here.

Antigen exposure through a disrupted skin barrier or through the gastrointestinal mucosa might be involved in the establishment of allergy and tolerance. Immune responses to such allergen exposures are likely to be modulated by nonspecific factors, such as gastrointestinal microflora, infectious exposure, other dietary factors, and possibly sunlight exposure. Source: Update on risk factors for food allergy

Sensitization to food allergens can occur in infants due to cutaneous exposure.

A series of studies have led to the hypothesis that infants can frequently have sensitization to food allergens through cutaneous exposure, especially if the skin barrier is impaired. Additional studies supporting this hypothesis were published in 2013 and 2014 by Brough et al, studying the distribution of peanut allergen in home environments and demonstrating relationships between early-life environmental peanut exposure and the development of PA, particularly in children who carry a filaggrin mutation. Source: Advances in food allergy in 2015

Food allergy present in childhood and with infants is now also recognized to develop in adulthood as adult-onset food allergy detailed here.

These findings indicated that several of the major food allergen groups commonly seen in childhood and those reported to persist into adulthood also are commonly found as triggers in the allergic reactions observed in newly diagnosed, adult-onset food allergy. Source: Prevalence and characteristics of adult-onset food allergy

2. Children or individuals with pre-existing hypersensitivity to the non-active components of the vaccine have a small risk of developing allergic reactions. For the remaining population, allergic reaction development due to those components of the vaccine is extremely rare and also studies have shown that food allergies are rarely contraindications to vaccine administration.

Children with allergy to non-active components of vaccines are rare. When they receive a vaccine containing the constituent to which they are hypersensitive, the risk of having an allergic reaction is small. However, this risk should not be neglected since a high number of doses are administered. Vaccinators should be able to identify children at risk for allergic reactions to vaccine. An allergological evaluation may be sought in selected cases to assess how and when vaccines may be given. In subjects at high risk, the vaccine can be safely given with precaution, when necessary giving administering doses, and with available materials and support for the treatment of anaphylaxis. This may avoid unnecessary incomplete vaccinations. Source: Vaccination in children with allergy to non active vaccine components

Immediate, systemic reactions – allergic or not – following vaccination with frequently used vaccines are very rare. The average reporting rate for immediate type reactions (ITR) in children and adolescents is 0.22 per 100000 doses of vaccines. 31% of these patients reported an ITR after the first vaccination. This observation suggests either a pre-sensitization to a vaccine component or non-immunologically mediated reaction. Source: Vaccine hypersensitivity – update and overview

3. It is also noted that since these reactions occur only in few patients or with lots of medications, and hence the medications or vaccines should not be withheld from those who have food allergies because they will be able to tolerate it. Decisions about revaccinations should also also made only by the physicians on the basis of a case-by-case risk/benefit analysis on the patient.

When a food protein appears as an unintentional contaminant, the amount, if any, that is present might be variable and might elicit reactions only from some lots of medication or only in some patients. In most circumstances these medications should not be routinely withheld from patients who have particular food allergies because most will tolerate the medications uneventfully. However, if a particular patient has had an apparent allergic reaction to the medication, potential allergy to the food component should be investigated. Source: Potential food allergens in medications,

Answer 3

I have searched on PubMed and have found no evidence other than theoretical that any food proteins contained in vaccines can cause food allergy to develop. The link in the claim just says that the IOM claimed it was possible but if you then reference their document, it just talks about possible mechanisms without quoting a single case report or controlled study.

On the other hand effectively the largest observational series in the world in a single population suggests that vaccines do not cause the development of allergies of any sort.

Experience in this country points in the same direction: in the German Democratic Republic (GDR), where vaccinations were mandatory and nearly all children were vaccinated, allergies were not an issue. They only started to increase in East Germany after reunification whilst the vaccination rates dropped.

https://www.rki.de/EN/Content/Institute/DepartmentsUnits/InfDiseaseEpidem/Div33/Objections_and_Responses.html

which suggests that environmental factors are responsible for the development of allergies and not vaccinations. The hygiene hypothesis is a popular medical theory as to why this happens.