Influenza vaccination effectiveness against influenza-associated hospitalization in children and the effects of repeated vaccination

Abstract

Background: Given concerns about the potential that influenza vaccine effectiveness (VE) might differ in recipients of repeated annual influenza vaccination, we aimed to estimate VE against influenza-associated hospitalization​ while investigating potential repeat vaccination effects.

Methods: We analyzed data from a test-negative design study conducted in three Hong Kong hospitals from ​​October 2015 through July 2025​​. Due to the absence of influenza circulation during the COVID-19 pandemic, the 2020/21 and 2021/22 seasons were excluded, leaving eight influenza seasons for subsequent analysis. PCR testing was used to identify influenza virus infections. We used conditional logistic regression to estimate influenza VE overall, by influenza type/subtype, and by influenza vaccination status in the preceding year (repeat vaccination status).

Results: We analyzed data on 34,237 children, among whom 5,245 (15.3%) tested positive for influenza. VE against influenza-associated hospitalization was 57.2% (95% confidence interval [CI]: 52.3%, 61.6%), with subtype-specific VE estimates of 67.7% (95% CI: 61.8%, 72.7%) for A(H1N1)pdm09, 60.6% (95% CI: 50.8%, 68.5%) for influenza B, and 37.2% (95% CI: 24.7%, 47.6%) for A(H3N2). The overall ΔVE (repeated VE - current only VE) was -13.6% (95% CI: -33.2%, 3.2%), indicating lower VE among repeatedly vaccinated children.

Conclusions: Current influenza vaccination programs provide substantial protection, but could be further improved by strategies that could mitigate repeat vaccination effects, and further research is needed to identify such strategies.

Keywords: A(H1N1)pdm09; influenza; repeat vaccination; vaccination; vaccine effectiveness.