M2-Deficient Single-Replication Influenza Vaccine-Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain.

Background: Current influenza vaccines are strain specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mismatched to circulating virus. The novel influenza vaccine candidate, M2-deficient single replication (M2SR), induces a broad, multi-effector immune response.
Methods: A phase 2 challenge study was conducted to assess the efficacy of an M2SR vaccine expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (Bris2007 M2SR H3N2; clade 1). Four weeks after vaccination, recipients were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b) and assessed for infection and clinical symptoms.
Results: Adverse events after vaccination were mild and similar in frequency for 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 recipients were infected after challenge, compared with 71% of placebo recipients. The subset of M2SR recipients with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs 71% of placebo recipients; P = .050) and reduced illness.
Conclusions: Study participants with vaccine-induced neutralizing antibodies were protected against infection and illness after challenge with an antigenically distinct virus. This is the first demonstration of vaccine-induced protection against a highly drifted H3N2 challenge virus.
Competing Interests: Potential conflicts of interest. B. V. and O. R. are employees of SGS Life Sciences. J. E. and R. A. are consultants to FluGen; R. B., H. G., and K. C. serve on FluGen’s Clinical Advisory Board; Y. K. and G. N. are founders of FluGen; and R. H., D. M., and P. B. are employees of FluGen.
(© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)