A synthetic influenza virus vaccine induces a cellular immune response that correlates with reduction in symptomatology and virus shedding in a randomized phase Ib live-virus challenge in humans

Abstract

Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n=16) or FLU-v (500 μg) and the adjuvant (n=16), both in saline. Twenty-one days later, FLU-v (n=15) and placebo (n=13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average±the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold±0.2-fold and 1.6-fold±0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold±3.9-fold versus 1.3- fold±0.1-fold higher than the negative-control value [average±SEM] for FLU-v versus the placebo [P=0.0005]). FLU-vspecific cellular responses also correlated with reductions in both viral titers (P=0.01) and symptom scores (P=0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads.