Abstract
From 2020, influenza viruses circulation was largely affected by the global coronavirus disease (COVID-19) pandemic, notably leading to the extinction of the B/Yamagata lineage and raising questions about the relevance of the quadrivalent influenza vaccine, which includes this lineage. Evaluating vaccine effectiveness (VE) against influenza infections is important to inform future vaccine programs. A test-negative case-control study was conducted in five tertiary hospitals in Hangzhou, the capital city of Zhejiang province, China, enrolling medically-attended patients aged >6 months who presented with influenza-like illness (ILI) from October 1, 2023, to March 31, 2024. The VE was estimated using multivariate logistic regression models adjusted for sex, age, influenza detection methods, and influenza testing timing. Of the 157,291 medically-attended ILI participants enrolled 56,704 (36%) tested positive for influenza. Adjusted overall VE against any medically-attended influenza infection was 48% (95% Confidence interval [CI]: 46%-51%). The overall VE of the trivalent inactivated influenza vaccine (IIV3) was 59% (95% CI: 50%-66%), followed by the trivalent live attenuated vaccine (LAIV3) (VE = 53%, 95% CI: 42%-62%) and quadrivalent inactivated influenza vaccine (IIV4) (VE = 47%, 95% CI: 45%-50%). IIV3 provided even better protection against medically-attended influenza B infection than IIV4 (VE = 87%, 95% CI: 81%-92% for IIV3 versus VE = 53%, 95% CI: 50%-57% for IIV4). In the 2023/24 season in Hangzhou, China, the influenza vaccine offered moderate protection during a major epidemic. The results supported the World Health Organization recommendation to exclude the B/Yamagata lineage antigen in quadrivalent influenza vaccines in 2023.