Post-Vaccination Anaphylaxis in Adults: A Systematic Review and Meta-Analysis

Pennisi F, D’Amelio AC, Cuciniello R, Borlini S, Mirzaian L, Ricciardi GE, Minerva M, Gianfredi V, Signorelli C. Vaccines. 2025; 13(1):37. https://doi.org/10.3390/vaccines13010037

Abstract

Background/Objectives: Vaccines have been recognized as one of the most effective public health interventions. However, vaccine-associated anaphylaxis, although rare, is a serious adverse reaction. The incidence of anaphylaxis related to non-COVID-19 vaccines in adults remains underreported. This systematic review and meta-analysis aim to estimate the incidence of post-vaccination anaphylaxis across various vaccines in adults. 

Methods: A comprehensive literature search of PubMed, Embase, Scopus, and Web of Science identified studies on anaphylaxis following vaccination in adults (≥18 years), excluding COVID-19 vaccines. PRISMA 2020 guidelines were followed. The protocol was registered in PROSPERO in advance (ID CRD42024566928). Random-effects and fixed-effects models were used to pool data and estimate the logit proportion, with the logit-transformed proportion serving as the effect size, thereby allowing for the calculation of event rates. 

Forest plot of the random-effects model assessing the logit proportion
among vulnerable populations (individuals with pre-existing allergies or
chronic conditions).In the forest plot, the effect sizes of
individual studies are represented in blue, while the overall
effect size is shown in green.

Results: A total of 37 studies were included in the systematic review, with 22 studies contributing to the meta-analysis, representing a combined population of 206,855,261 participants. Most studies focused on influenza vaccines (n = 15). Across all studies, 262 anaphylactic cases were reported, with 153 cases related to influenza vaccines, followed by herpes zoster virus vaccines (38 cases) and yellow fever vaccines (29 cases).

Td/Tdap vaccine had the lowest rate (0.0001 per 100,000 participants). The overall random-effects model yielded a logit proportion of −10.45 (95% CI: −12.09 to −8.82, p < 0.001), corresponding to an event rate of 2.91 events per 100,000 subjects (95% CI: 0.56 to 14.73). Sensitivity analysis showed a higher incidence for influenza, hepatitis vaccines, and in vulnerable populations.

Conclusions: Anaphylaxis following vaccination in adults is rare but varies by vaccine type. Strengthened monitoring and preparedness are essential, especially in non-medical settings, to ensure a rapid response to anaphylaxis and maintain public confidence in vaccination programs.

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