Hypersensitivity reactions to vaccines occur in 1 in 50,000 to 1 in 100,000 doses. Most are local reactions and allow for the completion of the vaccination series. Systemic reactions are a minority and may be immediate or delayed. Such reactions occur in response to one of the vaccine components, in most cases, though sometimes the vaccine antigen is the culprit.
Study: Hypersensitivity reactions to vaccines in children: from measles to SARS-CoV-2. Image Credit: Ira Lichi/Shutterstock
A new paper published in Pediatric Allergy and Immunity provides a useful overview of such reactions in relation to pediatric vaccines.
Allergy to egg protein in vaccines
A history of egg allergy is often cited as a reason to deny children vaccines such as the measles-mumps-rubella-varicella (MMR/MMRV) vaccine or influenza vaccine. Still, these contain 1ng, or less of egg albumin, and most allergic reactions to these vaccines are not related to egg allergy. Therefore, these may be used freely in such children, in contrast to the yellow fever vaccine containing more egg albumin. This mandates a pre-vaccine test for hypersensitivity to the vaccine by a skin prick and intradermal test in children with egg allergy.
Meanwhile, those who appear hypersensitive to the measles-mumps-rubella-varicella (MMR/MMRV) vaccine should be tested for allergy to the gelatin or other components, also found in yellow fever and Japanese encephalitis vaccines.
Gelatin, galactose, and milk allergies
Gelatin prick testing and gelatin-specific immunoglobulin E (IgE) testing should be done in children with a history suggestive of such allergy. If negative, an oral gelatin challenge is indicated. Alternatives in such children include gelatin-free vaccines or the use of a graded-dose vaccination series.
Since gelatin contains galactose-α-1,3-galactose (α-gal), vaccines such as zoster vaccine may require cautious use in children with α-gal allergy. Similarly, these children may develop hypersensitivity if they receive MMR, varicella, and diphtheria-tetanus-pertussis/ polio (DTaP/IPV) vaccines together.
Milk allergy may trigger such reactions to DTaP/IPV, as well as they contain traces of milk proteins, which mandates monitoring of such patients for one-hour post-vaccination. A history of latex allergy requires that this substance be avoided while administering the vaccine.
Allergic reactions to COVID-19 vaccines
With the messenger ribonucleic acid (mRNA) vaccines from Pfizer/BioNTech and Moderna directed against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the incidence of anaphylaxis, the most severe form of hypersensitivity reaction, was reported to be 11 per million doses with the former, and 2.5 per million doses with the latter. Over time, the incidence of anaphylaxis with the Pfizer vaccine declined to 4.7 and then to 0.46 per million doses by April 2021.
However, a prospective study cast some doubt on the reporting system responsible for this estimate by showing a comparable incidence of 0.027% and 0.023%, respectively, with Pfizer and Moderna. With the Johnson & Johnson's Janssen vaccine, which has been used in far smaller numbers, one case of anaphylaxis was reported.
Most such reactions were in females, and 86% occurred within half an hour with the Pfizer vaccine, vs. 90% within 15 minutes with Moderna. No deaths were reported from this cause.
Risk factors include food allergies and reactions to drugs, vaccines, cats, dogs, butterflies, jellyfish venom, polyethylene glycol polysorbate-80 (PEG-PS-80), other vaccine excipients, and contrast media containing iodine or gadolinium, as well as a history of hypersensitivity to the first dose.
However, many such reactions have occurred without any preceding risk factor, indicating the need to have emergency facilities at hand and a period of observation for at least half an hour in those with a history of anaphylaxis to other substances when taking the vaccine.
When it comes to a history of allergy to the first dose of a COVID-19 vaccine or its components, the presence of PEG-PS-80 is at fault in many cases. Skin testing for this chemical can trigger allergies, including anaphylaxis. The efficacy of desensitization therapy for this substance remains to be verified.
It is recommended that patients who have anaphylactic reactions to PEG-PS80 avoid the mRNA or other COVID-19 vaccines that contain this substance and do not take the second dose. Local reactions to the mRNA vaccines are typically delayed, and the second dose is usually well-tolerated in such patients.
The results show that a history of gelatin allergy is a risk factor for anaphylaxis or allergic reactions to the mRNA COVID-19 vaccines. The presence of α-gal allergy may also mandate caution. Other risk factors are also being listed, as given above.
Evaluation of the risk by an allergist should be carried out in the presence of a history of allergy to vaccine excipients or the first dose of a COVID-19 vaccine, and the findings should be the basis of a shared decision-making process between the doctor and the potential recipient before the second dose. More research is required to validate skin tests and desensitization protocols in those patients who have a confirmed history of hypersensitivity to the first dose, in order to make these vaccines safer.
Caffarelli, C. et al. (2022) "Hypersensitivity reactions to vaccines in children: from measles to SARS‐CoV‐2", Pediatric Allergy and Immunology, 33(S27), pp. 58-60. doi: https://doi.org/10.1111/pai.13631