The proportion of relative influenza vaccine efficacy (rVE) mediated by post-vaccination hemagglutination inhibition (HAI) and microneutralization (MN) antibody titers has not been evaluated. We compared rVE by influenza vaccine type and HAI and MN antibody titer against symptomatic influenza A(H3N2) infection in a randomized immunogenicity trial of quadrivalent cell culture-based (ccIIV4), recombinant (RIV4), and egg-based (eIIV4) influenza vaccines in US healthcare personnel, and estimated proportions of rVE mediated by antibody titers using causal mediation analysis. Cumulative influenza A(H3N2) incidence was 3.2%, 1.3% and 1% among ccIIV, eIIV4 and RIV4 recipients, respectively. Age-adjusted rVE estimates were not statistically significant. Higher MN and HAI titers against A(H3N2) vaccine and circulating viruses explained 97.9% and 15.8%, respectively, of rVE for RIV4 compared with ccIIV4, versus 1.7% and 12.6% of rVE for eIIV4 compared with ccIIV4, indicating MN titers to be used as correlates of protection against A(H3N2) for comparisons between cell-based influenza vaccines.
Zhong et al. (Thu,) studied this question.