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. Concl...