Comparison of antibody and T-cell responses elicited by licensed inactivated- and live-attenuated influenza vaccines against H3N2 hemagglutinin

T cells are being increasingly recognized as a significant component of influenza-specific immune responses in humans. Although an inactivated- and a live-attenuated influenza vaccine are now licensed for use in humans, their comparative ability to elicit T-cell responses against influenza is not well understood. Using the rapidly evolving H3N2 hemagglutinin (HA) as an antigenic model, we compared immune responses elicited by the trivalent inactivated influenza vaccine (TIV) and the live-attenuated influenza vaccine (LAIV) in a cohort of healthy adults 18–49 years of age. TIV elicited higher geometrical mean antibody titers than LAIV, whereas, LAIV elicited superior T-cell responses. Importantly, LAIV elicited higher magnitude T-cell responses toward the rapidly drifting variant region of HA that is prone to escape from antibody responses. These results have important implications for the deployment of influenza vaccines in years of antigenic mismatch and shift.