Combination of recombinant neuraminidase with cHA-based inactivated split vaccines improves the breadth of cross-reactivity and protection against influenza viruses in mice.

Current seasonal influenza virus vaccines are inefficient at inducing protective immune responses against drifted seasonal or emerging pandemic influenza viruses. A strategy to elicit more broadly cross-protective immune responses is to target conserved epitopes of the influenza virus, and the neuraminidase (NA) glycoprotein and the stalk domain of the hemagglutinin (HA) have become prime vaccine candidates. Sequential immunization with chimeric HA (cHA) antigens in which the immunodominant HA head domain has been replaced by HA head domains of exotic subtypes is able to re-focus the immune response to the HA stalk. Similarly, vaccination with recombinant NA (rNA) protein induces robust anti-NA responses. In this study, we show that sequential immunization with group 2 chimeric HA (cHA) inactivated split vaccines in combination with rN2 NA protein (rNA-N2-MPP) elicits superior immune responses and protection against a heterologous influenza virus in mice.