Humoral Immunogenicity of mRNA-1345 RSV Vaccine in Older Adults

J Infect Dis. 2024 Nov 15;230(5):e996-e1006. doi: 10.1093/infdis/jiae316.

Abstract

Background: The mRNA-1345 vaccine demonstrated efficacy against respiratory syncytial virus (RSV) disease with acceptable safety in adults aged ≥60 years in the ConquerRSV trial. Here, humoral immunogenicity results from the trial are presented.

Methods: This phase 2/3 trial randomly assigned adults (≥60 years) to mRNA-1345 50-µg encoding prefusion F (preF) glycoprotein (n = 17 793) vaccine or placebo (n = 17 748). RSV-A and RSV-B neutralizing antibody (nAb) and preF binding antibody (bAb) levels at baseline and day 29 postvaccination were assessed in a per-protocol immunogenicity subset (PPIS; mRNA-1345, n = 1515; placebo, n = 333).

Results: Day 29 nAb geometric mean titers (GMTs) increased 8.4-fold against RSV-A and 5.1-fold against RSV-B from baseline. Seroresponses (4-fold rise from baseline) in the mRNA-1345 groups were 74.2% and 56.5% for RSV-A and RSV-B, respectively. Baseline GMTs were lower among participants who met the seroresponse criteria than those who did not. mRNA-1345 induced preF bAbs at day 29, with a pattern similar to nAbs. Day 29 antibody responses across demographic and risk subgroups were generally consistent with the overall PPIS.

Conclusions: mRNA-1345 enhanced RSV-A and RSV-B nAbs and preF bAbs in adults (≥60 years) across various subgroups, including those at risk for severe disease, consistent with its demonstrated efficacy in the prevention of RSV disease.

Clinical trials registration: NCT05127434.

Keywords: RSV; binding antibody; immunogenicity; mRNA-1345; neutralizing antibody.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Double-Blind Method
  • Female
  • Humans
  • Immunity, Humoral
  • Immunogenicity, Vaccine
  • Male
  • Middle Aged
  • Respiratory Syncytial Virus Infections* / immunology
  • Respiratory Syncytial Virus Infections* / prevention & control
  • Respiratory Syncytial Virus Vaccines* / administration & dosage
  • Respiratory Syncytial Virus Vaccines* / genetics
  • Respiratory Syncytial Virus Vaccines* / immunology
  • Respiratory Syncytial Virus, Human* / genetics
  • Respiratory Syncytial Virus, Human* / immunology
  • mRNA Vaccines

Substances

  • Respiratory Syncytial Virus Vaccines
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • mRNA-1345 respiratory syncytial virus vaccine
  • mRNA Vaccines

Associated data

  • ClinicalTrials.gov/NCT05127434

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