Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study

Abstract

Study question: How safe is live attenuated influenza vaccine (LAIV), which contains egg protein, in young people with egg allergy?

Methods: In this open label, phase IV intervention study, 779 young people (2-18 years) with egg allergy were recruited from 30 UK allergy centres and immunised with LAIV. The cohort included 270 (34.7%) young people with previous anaphylaxis to egg, of whom 157 (20.1%) had experienced respiratory and/or cardiovascular symptoms. 445 (57.1%) had doctor diagnosed asthma or recurrent wheeze. Participants were observed for at least 30 minutes after vaccination and followed-up by telephone 72 hours later. Participants with a history of recurrent wheeze or asthma underwent further follow-up four weeks later. The main outcome measure was incidence of an adverse event within two hours of vaccination in young people with egg allergy.

Study answer and limitations: No systemic allergic reactions occurred (upper 95% confidence interval for population 0.47% and in participants with anaphylaxis to egg 1.36%). Nine participants (1.2%, 95% CI 0.5% to 2.2%) experienced mild symptoms, potentially consistent with a local, IgE mediated allergic reaction. Delayed events potentially related to the vaccine were reported in 221 participants. 62 participants (8.1%, 95% CI for population 6.3% to 10.3%) experienced lower respiratory tract symptoms within 72 hours, including 29 with parent reported wheeze. No participants were admitted to hospital. No increase in lower respiratory tract symptoms occurred in the four weeks after vaccination (assessed with asthma control test). The study cohort may represent young people with more severe allergy requiring specialist input, since they were recruited from secondary and tertiary allergy centres.

What this study adds: LAIV is associated with a low risk of systemic allergic reactions in young people with egg allergy. The vaccine seems to be well tolerated in those with well controlled asthma or recurrent wheeze.

Funding, competing interests, data sharing: This report is independent research commissioned and funded by a Department of Health policy research programme grant to the National Vaccine Evaluation Consortium. Additional funding was provided by the NIHR Clinical Research Networks, Health Protection Scotland (Edinburgh site), and Health & Social Care Services in Northern Ireland (Belfast site). PJT and MEL had support from the Department of Health for the submitted work; PJT has received research grants from the Medical Research Council and NIHR. No additional data available.Study registration ClinicalTrials.gov (NCT02111512) and the EU Clinical Trials Register EudraCT (2014-001537-92).

Fig 1 Flow of participants through study. 13 children were consented but not eligible for study: six had recently used antihistamines (family declined further study appointment), five refused after parental consent had been obtained; two had unstable asthma (and were given inactivated influenza vaccine instead)

Fig 2 Change in asthma control test (ACT) score at four weeks after immunisation with LAIV compared with baseline in young people with a history of asthma or recurrent wheeze