Domain-specific variation in hemagglutinin-specific T-cell responses elicited by licensed seasonal influenza vaccines (106.11)

Abstract

Persistent antigenic drift in influenza hemagglutinin (HA) results in the emergence of serologically novel influenza viruses that result in seasonal epidemics globally. While the globular domain of the HA antigen is the primary repository of drift mutations, the viral-fusion domain is highly conserved. T cells are being increasingly recognized as a significant component of influenza immunity in humans and may target variant regions of HA that are not effectively targeted by type-specific antibodies. While a trivalent inactivated influenza vaccine (TIV) and a live-attenuated influenza vaccine (LAIV) are now licensed for use in humans, their comparative ability to elicit T cell responses against influenza HA is not well understood: specifically, the relative magnitude of T cell responses elicited by TIV and LAIV and their domain-specificity toward HA regions is unknown. In this study, we systematically compare immune responses elicited by TIV and LAIV in a cohort of healthy adults (18 to 49 years old) against the rapidly evolving H3N2 HA antigen. Data suggests TIV elicits higher geometric mean antibody titers than LAIV; whereas, LAIV elicits superior T cell responses. Importantly, the two vaccines vary significantly in their ability to elicit T cell responses targeting the variant and conserved regions of HA. These results have important implications for the deployment of influenza vaccines in years of antigenic mismatch and shift.