Background: Current influenza vaccines are strain-specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mis-matched to circulating virus. The novel influenza vaccine candidate, M2SR (M2-deficient Single Replication), induces a broad, multi-effector immune response.

Methods: A phase 2 challenge study was conducted to assess efficacy of M2SR vaccine expressing HA and NA from A/Brisbane/10/2007 (H3N2, clade 1). Four weeks after vaccination subjects were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b), and assessed for infection and clinical symptoms.

Results: Adverse events following vaccination were mild and similar in frequency between placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR subjects were infected after challenge, compared to 71% of placebo subjects. The subset of M2SR subjects with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs. 71% of placebo subjects, P=0.0505) and reduced illness.

Conclusions: Subjects with vaccine-induced neutralizing antibodies were protected against infection and illness following challenge with an antigenically distinct virus. This is the first demonstration of vaccine-induced protection against a highly drifted H3N2 challenge virus.