J Fang

Influenza Hemagglutination-inhibition Antibody Titer as a Mediator of Vaccine-induced Protection for Influenza B

Background The hemagglutination inhibition (HAI) assay is an established correlate of protection for the inactivated influenza vaccine, but the proportion of vaccine-induced protection that is mediated by the post-vaccination HAI titer has not been assessed. Methods We used data from a randomized placebo-controlled trial of a split-virion inactivated influenza vaccine in children 6-17 years of age. Sera were collected before and 30 days after receipt of vaccination or placebo, and tested by the HAI assay against B/Brisbane/60/2008-like (B/Victoria lineage). We fitted Cox proportional hazards models to the time to laboratory-confirmed influenza B. We used causal mediation analysis to estimate the proportion of the total effect of vaccination that was mediated by higher HAI titers. Results We estimated that vaccine efficacy against confirmed B/Victoria infection was 68% (95% CI: 33%, 88%), and post-vaccination HAI titers explained 57% of the effect of vaccination on protection. Conclusions The majority of the effect of inactivated influenza vaccination in children is mediated by the increased HAI titer after vaccination, but other components of the immune response to vaccination may also play a role in protection and should be further explored. Causal mediation analysis provides a framework to quantify the role of various mediators of protection.