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

Abstract

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.

• Authors: Joseph Eiden, Bram Volckaert, Oleg Rudenko, Roger Aitchison, Renee Herber, Robert Belshe, Harry Greenberg, Kathleen Coelingh, David Marshall, Yoshihiro Kawaoka, Gabriele Neumann, Pamuk Bilsel
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 226 Issue 1 Pg. 83-90 (08 12 2022) ISSN: 1537-6613 [Electronic] United States
• PMID: 34323977 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Influenza Vaccines

Topics

• Antibodies, Neutralizing
• Antibodies, Viral
• Humans
• Immunity
• Influenza A Virus, H1N1 Subtype
• Influenza A Virus, H3N2 Subtype
• Influenza Vaccines
• Influenza, Human