Safety and immunogenicity of Multimeric-001 (M-001) followed by seasonal quadrivalent inactivated influenza vaccine in young adults - A randomized clinical trial.
2023 Apr 17
Journal Article
Authors:
Atmar, R.L.;
Bernstein, D.I.;
Winokur, P.;
Frey, S.E.;
Angelo, L.S.;
Bryant, C.;
Ben-Yedidia, T.;
Roberts, P.C.;
Sahly, H.M.El;
Keitel, W.A.
Secondary:
Vaccine
Volume:
41
Pagination:
2716-2722
Issue:
16
PMID:
36941155
URL:
https://pubmed.ncbi.nlm.nih.gov/36941155/
DOI:
10.1016/j.vaccine.2023.03.023
Keywords:
Antibodies, Viral; Double-Blind Method; Hemagglutination Inhibition Tests; Humans; Immunogenicity, Vaccine; Influenza B virus; Influenza Vaccines; Influenza, Human; Seasons; Vaccines, Combined; Vaccines, Inactivated; Young Adult
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).
