Intranasal M2SR (M2-Deficient Single Replication) Influenza Vaccine Induces Broadly Reactive Mucosal Antibody Production in Adults

Intranasal H3N2 M2SR vaccine induced cross-reactive mucosal IgA antibodies against a panel of H3N2 hemagglutinins, ranging from 1968 to 2014, in adults independent of baseline immune status. The breadth extended to potential pandemic strain H7N9, presumably through the hemagglutinin stem.Intranasal M2SR (M2-deficient single replication) influenza virus vaccine induces robust immune responses in animal models and humans. A high-throughput multiplexed platform was used to analyze hemagglutinin-specific mucosal antibody responses in adults after a single dose of H3N2 M2SR. Nasal swab specimens were analyzed for total and hemagglutinin-specific IgA. Significant dose-dependent increases in mucosal antibody responses to vaccine-matched and drifted H3N2 hemagglutinin were observed in persons vaccinated with M2SR regardless of baseline serum and mucosal immune status. These data suggest that M2SR induces broadly cross-reactive mucosal immune responses, which may provide better protection against drifted and newly emerging influenza strains.