Nature Communications (Aug 2024)

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

  • Lindsey R. Baden,
  • Hana M. El Sahly,
  • Brandon Essink,
  • Dean Follmann,
  • Gregory Hachigian,
  • Cynthia Strout,
  • J. Scott Overcash,
  • Susanne Doblecki-Lewis,
  • Jennifer A. Whitaker,
  • Evan J. Anderson,
  • Kathleen Neuzil,
  • Lawrence Corey,
  • Frances Priddy,
  • Joanne E. Tomassini,
  • Mollie Brown,
  • Bethany Girard,
  • Dina Stolman,
  • Veronica Urdaneta,
  • Xiaowei Wang,
  • Weiping Deng,
  • Honghong Zhou,
  • Avika Dixit,
  • Rituparna Das,
  • Jacqueline M. Miller,
  • the COVE Trial Consortium

DOI
https://doi.org/10.1038/s41467-024-50376-z
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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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.