Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases

Nat Commun. 2024 Aug 29;15(1):7469. doi: 10.1038/s41467-024-50376-z.

Abstract

Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites. The open-label (Parts B and C) primary objectives were evaluation of long-term safety and effectiveness of primary vaccination plus a 50-µg booster dose; immunogenicity was a secondary objective. Of 29,035 open-label participants, 19,609 received boosters (mRNA-1273 [n = 9647]; placebo-mRNA-1273 [n = 9952]; placebo [n = 10] groups). Booster safety was consistent with that reported for primary vaccination. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with a significant, 47.0% (95% CI : 39.0-53.9%) reduction of Omicron BA.1 incidence (24.6 [23.4 - 25.8] vs 46.4 [40.6 - 52.7]/1000 person-months). In an exploratory Cox regression model adjusted for time-varying covariates, a longer median interval between primary vaccination and boosting (mRNA-1273 [13 months] vs placebo-mRNA-1273 [8 months]) was associated with significantly lower, COVID-19 risk (24.0% [16.0% - 32.0%]) during Omicron BA.1 predominance. Boosting elicited greater immune responses against SARS-CoV-2 than primary vaccination, irrespective of prior SARS-CoV-2 infection. Primary vaccination and boosting with mRNA-1273 demonstrated acceptable safety, effectiveness and immunogenicity against COVID-19, including emergent variants.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273* / immunology
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / adverse effects
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunization, Secondary*
  • Immunogenicity, Vaccine
  • Male
  • Middle Aged
  • SARS-CoV-2* / immunology
  • Vaccination
  • Vaccine Efficacy
  • Young Adult

Substances

  • 2019-nCoV Vaccine mRNA-1273
  • COVID-19 Vaccines
  • Antibodies, Viral

Supplementary concepts

  • SARS-CoV-2 variants