tetano
Editor, Senior Moderator
Vaccine
. 2023 Mar 18;S0264-410X(23)00285-2.
doi: 10.1016/j.vaccine.2023.03.023. Online ahead of print.
Safety and immunogenicity of Multimeric-001 (M-001) followed by seasonal quadrivalent inactivated influenza vaccine in young adults - A randomized clinical trial
Robert L Atmar[SUP] 1 [/SUP], David I Bernstein[SUP] 2 [/SUP], Patricia Winokur[SUP] 3 [/SUP], Sharon E Frey[SUP] 4 [/SUP], Laura S Angelo[SUP] 5 [/SUP], Christopher Bryant[SUP] 6 [/SUP], Tammy Ben-Yedidia[SUP] 7 [/SUP], Paul C Roberts[SUP] 8 [/SUP], Hana M El Sahly[SUP] 9 [/SUP], Wendy A Keitel[SUP] 9 [/SUP]
Affiliations
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).
Keywords: Influenza vaccine; M-001; Polyfunctional CD4+ T cells; Randomized clinical trial; Serology.
. 2023 Mar 18;S0264-410X(23)00285-2.
doi: 10.1016/j.vaccine.2023.03.023. Online ahead of print.
Safety and immunogenicity of Multimeric-001 (M-001) followed by seasonal quadrivalent inactivated influenza vaccine in young adults - A randomized clinical trial
Robert L Atmar[SUP] 1 [/SUP], David I Bernstein[SUP] 2 [/SUP], Patricia Winokur[SUP] 3 [/SUP], Sharon E Frey[SUP] 4 [/SUP], Laura S Angelo[SUP] 5 [/SUP], Christopher Bryant[SUP] 6 [/SUP], Tammy Ben-Yedidia[SUP] 7 [/SUP], Paul C Roberts[SUP] 8 [/SUP], Hana M El Sahly[SUP] 9 [/SUP], Wendy A Keitel[SUP] 9 [/SUP]
Affiliations
- PMID: 36941155
- DOI: 10.1016/j.vaccine.2023.03.023
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).
Keywords: Influenza vaccine; M-001; Polyfunctional CD4+ T cells; Randomized clinical trial; Serology.