Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine.

Gustavo H, Dayan, Sanofi, Swiftwater, PA; Nadine, Rouphael, Emory University; Stephen R, Walsh, Harvard Medical School; Aiying, Chen, Sanofi, Swiftwater, PA; Nicole, Grunenberg, Fred Hutchinson Cancer Center; Mary, Allen, National Institute of Allergy and Infectious Diseases / National Institutes of Health; Johannes, Antony, Sanofi, Frankfurt, Germany; Kwaku Poku, Asante, Ghana Health Service; Amit, Suresh Bhate, Jeevan Rekha Hospital; Tatiana, Beresnev, National Institute of Allergy and Infectious Diseases / National Institutes of Health, Bethedsa; Matthew I, Bonaparte, Sanofi, Swiftwater, PA; Maria, Angeles Ceregido, GSK, Wavre, Belgium; Dmytro, Dobrianskyi, Medical Clinic Blagomed LLC, Kyiv, Ukraine; Bo, Fu, Sanofi, Swiftwater, PA; Marie-Helene, Grillet, Sanofi, Lyon, France; Maryam, Keshtkar-Jahromi, National Institute of Health, Rockville, Maryland; Michal, Juraska, Fred Hutchinson Cancer Center, Seattle; Jia, Jin Kee, Fred Hutchinson Cancer Center, Seattle; Hannah, Kibuuka, Makerere University Walter Reed Project; Marguerite, Koutsoukos, GSK, Wavre, Belgium; Roger, Masotti, Sanofi, Swiftwater, PA; Nelson L, Michael, Walter Reed Army Institute of Research; Humberto, Reynales, Centro de Attencion e Investigation Medica S.A.S, Columbia; Merlin L, Robb, The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda; Sandra M, Villagómez Martínez, Hospital de Temixco en acuerdo con el Instituto Nacional de Pediatria, México; Fredrick, Sawe, Kenya Medical Research Institute — US Army Medical Research; Lode, Schuerman, GSK, Wavre, Belgium; Tina, Tong, National Institute of Allergy and Infectious Diseases / National Institutes of Health, Bethedsa; John, Treanor, Tunnell Government Services in support of Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), Department of Health and Human Services (HHS), Washington, DC, USA; Anh T, Wartel, International Vaccine Institute, Seoul, South Korea; Carlos A, Diazgranados, Sanofi, Swiftwater, PA; Roman M, Chicz, Sanofi, Cambridge, MA; Sanjay, Gurunathan, Sanofi, Swiftwater, PA; Stephen, Savarino, Sanofi, Swiftwater, PA; Saranya, Sridhar, Sanofi, Reading, UK

Persistent URL

https://open.library.emory.edu/purl/351hhmgrtf-emory

Last modified

09/19/2025

Type of Material

Article

Authors

Gustavo H Dayan, Sanofi, Swiftwater, PA

Nadine Rouphael, Emory University

Stephen R Walsh, Harvard Medical School

Aiying Chen, Sanofi, Swiftwater, PA

Nicole Grunenberg, Fred Hutchinson Cancer Center

Mary Allen, National Institute of Allergy and Infectious Diseases / National Institutes of HealthJohannes Antony, Sanofi, Frankfurt, GermanyKwaku Poku Asante, Ghana Health ServiceAmit Suresh Bhate, Jeevan Rekha HospitalTatiana Beresnev, National Institute of Allergy and Infectious Diseases / National Institutes of Health, BethedsaMatthew I Bonaparte, Sanofi, Swiftwater, PAMaria Angeles Ceregido, GSK, Wavre, BelgiumDmytro Dobrianskyi, Medical Clinic Blagomed LLC, Kyiv, UkraineBo Fu, Sanofi, Swiftwater, PAMarie-Helene Grillet, Sanofi, Lyon, FranceMaryam Keshtkar-Jahromi, National Institute of Health, Rockville, MarylandMichal Juraska, Fred Hutchinson Cancer Center, SeattleJia Jin Kee, Fred Hutchinson Cancer Center, SeattleHannah Kibuuka, Makerere University Walter Reed ProjectMarguerite Koutsoukos, GSK, Wavre, BelgiumRoger Masotti, Sanofi, Swiftwater, PANelson L Michael, Walter Reed Army Institute of ResearchHumberto Reynales, Centro de Attencion e Investigation Medica S.A.S, ColumbiaMerlin L Robb, The Henry M Jackson Foundation for the Advancement of Military Medicine, BethesdaSandra M Villagómez Martínez, Hospital de Temixco en acuerdo con el Instituto Nacional de Pediatria, MéxicoFredrick Sawe, Kenya Medical Research Institute — US Army Medical ResearchLode Schuerman, GSK, Wavre, BelgiumTina Tong, National Institute of Allergy and Infectious Diseases / National Institutes of Health, BethedsaJohn Treanor, Tunnell Government Services in support of Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), Department of Health and Human Services (HHS), Washington, DC, USAAnh T Wartel, International Vaccine Institute, Seoul, South KoreaCarlos A Diazgranados, Sanofi, Swiftwater, PARoman M Chicz, Sanofi, Cambridge, MASanjay Gurunathan, Sanofi, Swiftwater, PAStephen Savarino, Sanofi, Swiftwater, PASaranya Sridhar, Sanofi, Reading, UK

Language

English

Date

2023-01-13

Publisher

medRxiv

Publication Version

Preprint (Prior to Peer Review)

Copyright Statement

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

License

Creative Commons Attribution-NonCommercial 4.0 International

Final Published Version (URL)

http://dx.doi.org/10.1101/2022.12.05.22282933

Title of Journal or Parent Work

medRxiv

Grant/Funding Information

The NIAID provides grant funding to the HIV Vaccine Trials Network (HVTN) Leadership and Operations Center (UM1 AI 68614HVTN), the Statistics and Data Management Center (UM1 AI 68635), the HVTN Laboratory Center (UM1 AI 68618), the HIV Prevention Trials Network Leadership and Operations Center (UM1 AI 68619), the AIDS Clinical Trials Group Leadership and Operations Center (UM1 AI 68636), and the Infectious Diseases Clinical Research Consortium leadership group 5 (UM1 AI 148684-03).
Funding was provided by Sanofi and by federal funds from the Biomedical Advanced Research and Development Authority, part of the office of the Administration for Strategic Preparedness and Response at the U.S. Department of Health and Human Services under contract number HHSO100201600005I, and in collaboration with the U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense under contract number W15QKN-16-9-1002. The views presented here are those of the authors and do not purport to represent those of the Department of the Army. This work was done in collaboration with GSK, who provided access to, and use of, the AS03 Adjuvant System.

Abstract

BACKGROUND: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. METHODS: We conducted a global Phase 3, multi-stage efficacy study ( NCT04904549 ) among adults aged ≥18 years. Participants were randomized 1:1 to receive two intramuscular injections 21 days apart of a bivalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (5 μg of ancestral (D614) and 5 μg of B.1.351 [beta] variant spike protein) or placebo. Symptomatic COVID-19 was defined as laboratory-confirmed COVID-19 with COVID-19-like illness (CLI) symptoms. The primary efficacy endpoint was the prevention of symptomatic COVID-19 ≥14 days after the second injection (post-dose 2 [PD2]). RESULTS: Between 19 Oct 2021 and 15 Feb 2022, 12,924 participants received ≥1 study injection. 75% of participants were SARS-CoV-2 non-naïve. 11,416 participants received both study injections (efficacy-evaluable population [vaccine, n=5,736; placebo, n=5,680]). Up to 15 March 2022, 121 symptomatic COVID-19 cases were reported (32 in the vaccine group and 89 in the placebo group) ≥14 days PD2 with a vaccine efficacy (VE) of 64.7% (95% confidence interval [CI] 46.6; 77.2%). VE was 75.1% (95% CI 56.3; 86.6%) in non-naïve and 30.9% (95% CI -39.3; 66.7%) in naïve participants. Viral genome sequencing identified the infecting strain in 68 cases (Omicron [BA.1 and BA.2 subvariants]: 63; Delta: 4; Omicron and Delta: 1). The vaccine was well-tolerated and had an acceptable safety profile. CONCLUSIONS: A bivalent vaccine conferred heterologous protection against symptomatic infection with newly emergent Omicron (BA.1 and BA.2) in non-naïve adults 18-59 years of age. CLINICALTRIALSGOV: NCT04904549.

Author Notes