Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase
Hana M El Sahly, Lindsey R Baden, Brandon Essink, Susanne Doblecki-Lewis, Judith M Martin, Evan J Anderson, Thomas B Campbell, Jesse Clark, Lisa A Jackson, Carl J Fichtenbaum, Marcus Zervos, Bruce Rankin, Frank Eder, Gregory Feldman, Christina Kennelly, Laurie Han-Conrad, Michael Levin, Kathleen M Neuzil, Lawrence Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, Laura Polakowski, John R Mascola, Julie E Ledgerwood, Barney S Graham, Allison August, Heather Clouting, Weiping Deng, Shu Han, Brett Leav, Deb Manzo, Rolando Pajon, Florian Schödel, Joanne E Tomassini, Honghong Zhou, Jacqueline Miller, COVE Study Group
Abstract
Background: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.
Methods: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021.
Results: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified.
Conclusions: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).
Copyright © 2021 Massachusetts Medical Society.
Figures
References
- Baden LR, El Sahly HM, Essink B, et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-416.
- Johnson & Johnson COVID-19 vaccine authorized by U.S. FDA for emergency use — first single-shot vaccine in fight against global pandemic. New Brunswick, NJ: Johnson & Johnson, February27, 2021. ().
- Polack FP, Thomas SJ, Kitchin N, et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-2615.
- Sadoff J, Le Gars M, Shukarev G, et al.Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. N Engl J Med 2021;384:1824-1835.
- Dagan N, Barda N, Kepten E, et al.BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021;384:1412-1423.
- Maternal, neonatal, and child health services during COVID-19. Atlanta: Centers for Disease Control and Prevention, November5, 2020. ().
- Thompson MG, Burgess JL, Naleway AL, et al.Prevention and attenuation of Covid-19 with the BNT162b2 and mRNA-1273 vaccines. N Engl J Med 2021;385:320-329.
- Thompson MG, Burgess JL, Naleway AL, et al.Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers — eight U.S. locations, December 2020–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:495-500.
- Tenforde MW, Olson SM, Self WH, et al.Effectiveness of Pfizer-BioNTech and Moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years — United States, January–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:674-679.
- Pawlowski C, Lenehan P, Puranik A, et al.FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. Med (N Y) 2021;2(8):979-992.e8.
- Corbett KS, Edwards D, Leist SR, et al.SARS-CoV-2 mRNA vaccine development enabled by prototype pathogen preparedness. June11, 2020. (). preprint.
- Haas EJ, Angulo FJ, McLaughlin JM, et al.Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet 2021;397:1819-1829.
- Planas D, Bruel T, Grzelak L, et al.Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med 2021;27:917-924.
- Abu-Raddad LJ, Chemaitelly H, Butt AA. Effectiveness of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants. N Engl J Med 2021;385:187-189.
- Bernal JL, Andrews N, Gower C, et al.Effectiveness of COVID-19 vaccines against the B.1.617.2 variant. May24, 2021. (). preprint.
- Marshall M, Ferguson ID, Lewis P, et al.Symptomatic acute myocarditis in 7 adolescents after Pfizer-BioNTech COVID-19 vaccination. Pediatrics 2021;148(3):e2021052478-e2021052478.
- Thomas SJ, Moreira ED, Kitchin N, et al.Six month safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. July28, 2021. (). preprint.
- Tenforde MW, Patel MM, Ginde AA, et al.Effectiveness of SARS-CoV-2 mRNA vaccines for preventing Covid-19 hospitalizations in the United States. Clin Infect Dis 2021August6(Epub ahead of print).
- Jones NK, Rivett L, Seaman S, et al.Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection. Elife 2021;10:e68808-e68808.
- Tande AJ, Pollock BD, Shah ND, et al.Impact of the COVID-19 vaccine on asymptomatic infection among patients undergoing pre-procedural COVID-19 molecular screening. Clin Infect Dis 2021March10(Epub ahead of print).
- Collier AY, McMahan K, Yu J, et al.Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA 2021;325:2370-2380.
- Shimabukuro TT, Kim SY, Myers TR, et al.Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N Engl J Med 2021;384:2273-2282.
- Ali K, Berman G, Zhou H, et al.Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. N Engl J Med. DOI: 10.1056/NEJMoa2109522.
- Frenck RW Jr, Klein NP, Kitchin N, et al.Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021;385:239-250.
- Haidar G, Agha M, Lukanski A, et al.Immunogenicity of COVID-19 vaccination in immunocompromised patients: an observational, prospective cohort study interim analysis. June30, 2021. (). preprint.
- Hadjadj J, Planas D, Ouedrani A, et al.Immunogenicity of BNT162b2 vaccine against the alpha and delta variants in immunocompromised patients. August9, 2021. (). preprint.
Source: PubMed