Vaccination is an important and effective method to develop active immunity against certain pathogens. It helps to prevent or reduce the risks of developing certain infectious diseases as well as moderating disease severity. However, the administration of certain vaccines, including influenza, measles-mumps- rubella (MMR), measles-mumps-rubellavaricella (MMR-V) and yellow fever vaccines, has historically been relatively, if not absolutely, contra-indicated in egg-allergic individuals. This is because these vaccines are developed in chicken egg embryos or chicken cell fibroblasts, raising the concern that egg proteins (notably ovalbumin) in these vaccines may trigger an immediate allergic reaction in egg-allergic individuals. As a result, previous vaccination guidelines and vaccine product information have recommended avoidance of influenza and MMR or MMR-V vaccines in individuals with a history of anaphylactic reaction to egg exposure.

Local epidemiological studies have shown that 0.4%-0.7% of Hong Kong children were reported by their parents to have had an adverse reaction to intake of a hen’s egg.1 2 No local data for the adult population are available. However, it is important to differentiate between adverse reactions and genuine egg allergy, especially when deciding the need for vaccine avoidance. A recent United Kingdom multi-centre study found that more than a third of patients with suspected egg allergy who were referred to a tertiary allergy centre for vaccination were not actually egg allergic, and all were vaccinated successfully.3

Despite the paucity of evidence, there remains some concern that administration of vaccines that could contain egg proteins, notably ovalbumin, might cause allergic reactions in egg-allergic subjects. The Centre for Health Protection recommends that mildly egg-allergic individuals can safely receive inactivated influenza vaccine in a primary care setting. However, those with confirmed or suspected egg allergy who have experienced severe reactions should be seen by an allergist/immunologist for evaluation of their egg allergy prior to administration of inactivated influenza vaccine.4

Recently published international guidelines have updated their recommendations regarding the administration of vaccines to egg-allergic individuals. This joint consensus statement by the Hong Kong Institute of Allergy and the Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases summarises recent updates and provides recommendations for local general practitioners and paediatricians. For practical reasons, this guideline will only cover influenza and MMR/MMR-V vaccines.

Yellow fever vaccine is less commonly administered and is commonly propagated in hens’ eggs. Specialist evaluation is recommended prior to vaccination for evaluation of suspected egg allergies with vaccine skin testing or consideration for desensitisation.3 An egg-free yellow fever formulation is available as an alternative.

The Q fever vaccine is not available in Hong Kong and therefore is not covered in this guideline.

Influenza vaccination is well known to be effective in preventing infections caused by influenza viruses and in reducing the risk of developing complications. We reviewed the product information recommendations of Vaxigrip (Sanofi Pasteur SA, Lyon, France), Fluarix Tetra (GlaxoSmithKline Biologicals, Dresden, Germany), and FluQuadri (Sanofi Pasteur SA, Lyon, France). All recommended that patients with egg or chicken protein hypersensitivity are contra-indicated to receive their vaccines. However, upon direct communication with the respective pharmaceutical companies, all of them were reported to contain <0.1 ug/mL of ovalbumin in their vaccines. Therefore, we disagree with their recommendations.

Moneret-Vautrin et al5 reported that only 1% of egg-allergic patients would develop allergic reactions at a threshold as low as 1 mg. As the quantity of ovalbumin in influenza vaccines is ≤1 μg/dose, such a level of egg protein in influenza vaccines is very unlikely to trigger an allergic response in this group of patients. Thus, despite the product information recommendations and the trace amounts of ovalbumin present in these influenza vaccines, they should be safe for egg-allergic individuals, including those with a history of anaphylaxis to egg proteins.

Our view is supported by numerous international guidelines on administration of influenza vaccines to egg-allergic individuals, summarised in the Table.6 7 8 9 10 11 12

The MMR and MMR-V vaccines are safe and effective in preventing mumps, measles, rubella, and varicella. The vaccination schedule in Hong Kong recommends that the first dose be administered at age 1 year and the second dose at Primary 1 (age 5-6 years).13 We reviewed the product information recommendations of two MMR-V vaccines available in Hong Kong: Priorix-Tetra (GlaxoSmithKline plc [GSK], Brentford, UK) and ProQuad (Merck & Co, Inc, Kenilworth [NJ], US). The manufacturers of both of these products recommend that patients with severe allergic reactions after egg ingestion should take extra precaution when receiving the vaccines. However, in direct communication with the manufacturers, GSK replied that Priorix-Tetra may contain traces of egg protein but the amount is not measured in the final product. In contrast, Merck replied that internal analysis was done for ProQuad for its egg protein content; however, they refused to disclose the information as they consider it proprietary. We disagree with their recommendations. The Table summarises international recommendations for administration of MMR/MMR-V vaccines to egg-allergic individuals.6 11 14 15 16 It is recommended that all patients, including those with suspected or confirmed egg allergy, should receive the MMR/MMR-V vaccination as a matter of routine in primary care, as the vaccine does not contain egg allergen.

1. All patients with suspected or confirmed egg allergy should receive the MMR/MMR-V vaccination as a matter of routine in primary care.
2. Influenza vaccines can be safely administered, and are recommended, for disease prevention in egg-allergic individuals. They are recommended to be administered in an out-patient or ambulatory setting.
3. Only those patients who have previously required admission to an intensive care unit for severe anaphylaxis to egg should be referred to an allergist for further evaluation prior to influenza vaccination.
4. Should there be any significant concerns from patients, parents or health care professionals, health care professionals who are capable of recognising signs and symptoms of an allergic reaction can provide 15 to 30 minutes of monitoring following vaccination.
5. Specialist evaluation is recommended prior to yellow fever vaccination in egg-allergic individuals (Fig).
6. Individuals who have developed or are suspected to have developed an allergic reaction to the vaccine or other vaccine components (such as gelatine or neomycin) should not undergo further vaccination with these products. Referral to an allergy specialist for further evaluation can be considered (Fig).
7. A significant number of suspected egg-allergic patients may be misdiagnosed, so referral to an allergist for evaluation may be considered.

GT Chua and PH Li drafted the main text of the article, including the tables and figures. E Lai and V Ngai offered their expert opinion as clinical pharmacists and contacted pharmaceutical companies regarding the contents of the vaccines. MHK Ho, MYW Kwan, FYS Yau, TF Leung, and TH Lee contributed to the concept, analysis, and critical revision of the article.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

All authors have disclosed no conflicts of interest. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

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