Safety and Immunogenicity of Multimeric-001 (M-001) Followed by Seasonal Quadrivalent Inactivated Influenza Vaccine in Young Adults – a Randomized Clinical Trial

Authors

Robert L Atmar
David I Bernstein
Patricia Winokur
Sharon E Frey
Laura S Angelo
Christopher Bryant
Tammy Ben-Yedidia
Paul C Roberts
Hana M El Sahly
Wendy A Keitel

Publication Date

4-17-2023

Journal

Vaccine

DOI

10.1016/j.vaccine.2023.03.023

PMID

36941155

PMCID

PMC10396309

PubMedCentral® Posted Date

4-17-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Young Adult, Influenza Vaccines, Seasons, Antibodies, Viral, Influenza, Human, Influenza B virus, Vaccines, Inactivated, Vaccines, Combined, Hemagglutination Inhibition Tests, Double-Blind Method, Immunogenicity, Vaccine, Influenza vaccine, M-001, hemagglutination inhibition, neutralization, CD4+ T cells, CD8+ T cells

Abstract

BACKGROUND: The continuing evolution of influenza viruses poses a challenge to vaccine prevention, highlighting the need for a universal influenza vaccine. We evaluated the safety and immunogenicity of one such candidate, Multimeric-001 (M-001), when used as a priming vaccine prior to administration of quadrivalent inactivated influenza vaccine (IIV4).

METHODS: Healthy adults 18 to 49 years of age were enrolled in a phase 2 randomized, double-blind placebo-controlled trial. Participants received two doses of either 1.0-mg M-001 or saline placebo (60 per study arm) on Days 1 and 22 followed by a single dose of IIV4 on about Day 172. Safety, reactogenicity, cellular immune responses and influenza hemagglutination inhibition (HAI) and microneutralization (MN) were assessed.

RESULTS: The M-001 vaccine was safe and had an acceptable reactogenicity profile. Injection site tenderness (39% post-dose 1, 29% post-dose 2) was the most common reaction after M-001 administration. Polyfunctional CD4+ T cell responses (perforin-negative, CD107α-negative, TNF-α+, IFN-γ+, with or without IL-2) to the pool of M-001 peptides increased significantly from baseline to two weeks after the second dose of M-001, and this increase persisted through Day 172. However, there was no enhancement of HAI or MN antibody responses among M-001 recipients following IIV4 administration.

CONCLUSIONS: M-001 administration induced a subset of polyfunctional CD4+ T cells that persisted through 6 months of follow-up, but it did not improve HAI or MN antibody responses to IIV4. (clinicaltrials.gov NCT03058692).