A single cycle influenza virus coated in H7 hemagglutinin provides heterotypic protection and neutralising antibody responses to both glycoproteins

Abstract

A non-replicating form of pseudotyped influenza virus, inactivated by suppression of the hemagglutinin signal sequence (S-FLU), can act as a broadly protective vaccine. We show that vaccination in the lung induced a strong local CD8 T cell response and protected against heterosubtypic X31 (H3N2) virus and highly virulent PR8 (H1N1), but not influenza B virus. Lung vaccination also induced a strong neutralising antibody response to the encoded neuraminidase. If given at higher dose in the periphery, H7 S-FLU induced a specific neutralising antibody response to H7 hemagglutinin coating the particle. Polyvalent vaccination with mixed H7 S-FLU induced a broadly neutralising antibody response to all four H7 strains. S-FLU is a versatile vaccine candidate that could be rapidly mobilized ahead of a new pandemic threat.