Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases.
Baden Lindsey R, El Sahly Hana M, Essink Brandon, Follmann Dean, Hachigian Gregory, Strout Cynthia, Overcash J Scott, Doblecki-Lewis Susanne, Whitaker Jennifer A, Anderson Evan J, Neuzil Kathleen, Corey Lawrence, Priddy Frances, Tomassini Joanne E, Brown Mollie, Girard Bethany, Stolman Dina, Urdaneta Veronica, Wang Xiaowei, Deng Weiping, Zhou Honghong, Dixit Avika, Das Rituparna, Miller Jacqueline M, COVE Trial Consortium
Nature communications · 2024 · PMID 39209823
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.