Vaccination with Deglycosylated Modified Hemagglutinin Broadly Protects against Influenza Virus Infection in Mice and Ferrets

Recent efforts have been directed toward the development of universal influenza vaccines inducing broadly neutralizing antibodies to conserved antigenic supersites of Hemagglutinin (HA). Although several studies raise the importance of glycosylation in HA antigen design, whether this theory can be widely confirmed remains unclear; which influenza HA with an altered glycosylation profile could impact the amplitude and focus of the host immune response. Here, we evaluated the characteristics and efficacy of deglycosylated modified HA proteins, including monoglycosylated HA (HA(mg)), unglycosylated HA (HA(ug)), and fully glycosylated HA (HA(fg)), without treatment with H3N2 Wisconsin/67/2005. Our results showed that HA(ug) could induce a cross-strain protective immune response in mice against both H3N2 and H7N9 subtypes with better antibody-dependent cellular cytotoxicity (ADCC) than the HA(mg)- and HA(fg)-immunized groups, which suggested that highly conserved epitopes that were masked by surface glycosylation may be exposed and thus promote the induction of broad antibodies that recognize the hidden epitopes. This strategy may also supplement the direction of deglycosylated modified HA for universal influenza vaccines.