Prime-boost vaccination with a live attenuated influenza vaccine elicits T cell-mediated cross-strain protective immunity (P4287)

Abstract

Abstract Antigen drift and shift of influenza viruses requires frequent reformulation of influenza vaccines. This stresses the need for a universal influenza vaccine. In this study, mice were vaccinated with the trivalent live attenuated (LAIV, nasal spray FluMist) and inactivated (TIV, flu shot FluZone) influenza vaccines by 1-3 dose prime-boost vaccination regimens. While vaccination with both LAIV and TIV elicited strong humoral responses, only LAIV induced significant protection against challenge with the non-vaccine strain H1N1 PR8 influenza virus. Furthermore, protective immunity against PR8 was dose-dependent. Of note, IL-2 and IFN-γ cytokine secretion in the lung alveolar fluid were significantly elevated in mice immunized with LAIV. Moreover, T cell depletion of LAIV immunized mice compromised protection, indicating that T cell-mediated immunities were required. In contrast, passive transfer of sera from mice immunized with LAIV into naïve mice failed to protect against PR8 challenge. To verify these results, we performed virus neutralization assays in vitro and confirmed that LAIV did not induce cross-strain neutralizing antibodies against PR8 virus. Finally, we showed that 3 doses of LAIV also provided protection against challenge with additional two heterologous viruses FM/47 (H1N1) and HK/68 (H3N2). These results support the potential use of the LAIV as a universal influenza vaccine under prime-boost vaccination regimen.