Intranasal M2SR (M2-deficient Single Replication) H3N2 Influenza Vaccine Provides Enhanced Mucosal and Serum Antibodies In Adults.

BACKGROUND: We previously demonstrated that an intranasal dose of 108 TCID50 M2SR (M2-deficient single replication) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection.

METHODS: Sero-susceptible subjects ages 18-49 years were randomized to receive two doses (108-109TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines (ClinicalTrials.gov number NCT03999554).

RESULTS: The vaccine was well-tolerated at all dose levels. Against Belgium2015,  ≥ 2-fold increases in MN antibodies were noted among 40% (95% CI 24.9-56.7) of subjects following a single 108 TCID50 M2SR dose and among 80.6% (95% CI 61.4-92.3) after 109 dose (P < 0.001). A single 109 TCID50 dose of M2SR generated ≥4-fold HAI seroconversion against the vaccine strain in 71% (95% CI 52.0-85.8) of recipients. Mucosal and cellular immune responses were also induced.

CONCLUSIONS: These results indicate that M2SR may provide substantial protection against infection with highly drifted strains of H3N2 influenza.