1. Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group studyResearch in context
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Guy de Bruyn, Joyce Wang, Annie Purvis, Martin Sanchez Ruiz, Haritha Adhikarla, Saad Alvi, Matthew I. Bonaparte, Daniel Brune, Agustin Bueso, Richard M. Canter, Maria Angeles Ceregido, Sachin Deshmukh, David Diemert, Adam Finn, Remi Forrat, Bo Fu, Julie Gallais, Paul Griffin, Marie-Helene Grillet, Owen Haney, Jeffrey A. Henderson, Marguerite Koutsoukos, Odile Launay, Federico Martinon Torres, Roger Masotti, Nelson L. Michael, Juliana Park, Doris Maribel Rivera-Medina, Natalya Romanyak, Chris Rook, Lode Schuerman, Lawrence D. Sher, Fernanda Tavares-Da-Silva, Ashley Whittington, Roman M. Chicz, Sanjay Gurunathan, Stephen Savarino, Saranya Sridhar, Allaw Mohammed, Babin Valérie, Babyak Jennifer, Ines Ben-Ghezala, Thomas Breuer, Corinne Breymeier, Anne Conrad, Ciarrah Holmqvist, Cristiana Costa-Araujo, Florence Coux, Christine Dellanno, Bertrand Dussol, Brandon Essink, Jesús Garrido, Pierre-Olivier Girodet, Claudia Gonzalez, Marie-Ange Grosbois, Justin Hammond, Chelsea He, Ciarrah Homlqvist, Kathy Hudzina, Mark Hutchens, Peta-Gay Jackson Booth, Arnel Joaquin, Rama Kandasamy, Jennifer Kasztejna, Michael Keefer, Murray Kimmel, Matthew Kresge, Fabrice Laine, Maeva Lefebvre, Denise Lopez, Malaborbor Perpetua Lourdes, Zoha Maakaroun-Vermesse, Caitlin Malishchak, Lisa Menard, Sandra Mendoza, Patrick Moore, Mounika Mulamalla, Patrick Mulholland, Jean-Francois Nicolas, Onyema Ogbuagu, Juan Ortiz, Ana Paula Perroud, Gina Peyton, Ya-Fen Purvis, Vanessa Raabe, Enrique Rivas, Nadine Rouphael, Beatrice Roy, Lola Sagot, Nessryne Sater, Howard Schwartz, Randall Severance, Jiayuan Shi, Magdalena Sobieszczyk, Charlene Stevens, Tran Phuong Thuy, Ramy Toma, Tina Tong, Sophie Tourneux, John Treanor, Núria Turet, Rachel Froget, Stephen Walsh, Judith White, Victor del Campo Perez, Lina Perez Breva, Pablo Rojo Conejo, Maria Belen Ruiz Antoraz, Toong Chin, Charlotte Fribbens, Adrian Phillipson, Rachel Kaminski, Stevan Emmett, Corey Hebert, Thomas Birch, Russell Roberson, Jeffrey Zacher, Sophie Gelu-Maury, Loron Loryne, and Yvonne Davis
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AS03 adjuvant ,Beta ,Booster ,B.1.351 ,COVID-19 ,CoV2 preS dTM-AS03 ,Medicine (General) ,R5-920 - Abstract
Summary: Background: In a parallel-group, international, phase 3 study (ClinicalTrials.gov NCT04762680), we evaluated prototype (D614) and Beta (B.1.351) variant recombinant spike protein booster vaccines with AS03-adjuvant (CoV2 preS dTM-AS03). Methods: Adults, previously primed with mRNA (BNT162b2, mRNA-1273), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or protein (CoV2 preS dTM-AS03 [monovalent D614; MV(D614)]) vaccines were enrolled between 29 July 2021 and 22 February 2022. Participants were stratified by age (18–55 and ≥ 56 years) and received one of the following CoV2 preS dTM-AS03 booster formulations: MV(D614) (n = 1285), MV(B.1.351) (n = 707) or bivalent D614 + B.1.351 (BiV; n = 625). Unvaccinated adults who tested negative on a SARS-CoV-2 rapid diagnostic test (control group, n = 479) received two primary doses, 21 days apart, of MV(D614). Anti-D614G and anti-B.1.351 antibodies were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay 14 days post-booster (day [D]15) in 18–55-year-old BNT162b2-primed participants and compared with those pre-booster (D1) and on D36 in 18–55-year-old controls (primary immunogenicity endpoints). PsVN titers to Omicron BA.1, BA.2 and BA.4/5 subvariants were also evaluated. Safety was evaluated over a 12-month follow-up period. Planned interim analyses are presented up to 14 days post-last vaccination for immunogenicity and over a median duration of 5 months for safety. Findings: All three boosters elicited robust anti-D614G or -B.1.351 PsVN responses for mRNA, adenovirus-vectored and protein vaccine-primed groups. Among BNT162b2-primed adults (18–55 years), geometric means of the individual post-booster versus pre-booster titer ratio (95% confidence interval [CI]) were: for MV (D614), 23.37 (18.58–29.38) (anti-D614G); for MV(B.1.351), 35.41 (26.71–46.95) (anti-B.1.351); and for BiV, 14.39 (11.39–18.28) (anti-D614G) and 34.18 (25.84–45.22 (anti-B.1.351). GMT ratios (98.3% CI) versus post-primary vaccination GMTs in controls, were: for MV(D614) booster, 2.16 (1.69; 2.75) [anti-D614G]; for MV(B.1.351), 1.96 (1.54; 2.50) [anti-B.1.351]; and for BiV, 2.34 (1.84; 2.96) [anti-D614G] and 1.39 (1.09; 1.77) [anti-B.1.351]. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 (across priming vaccine subgroups), Omicron BA.1 (BNT162b2-primed participants) and Omicron BA.4/5 (BNT162b2-primed participants and MV D614-primed participants). Similar patterns in antibody responses were observed for participants aged ≥56 years. Reactogenicity tended to be transient and mild-to-moderate severity in all booster groups. No safety concerns were identified. Interpretation: CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. Funding: Sanofi and Biomedical Advanced Research and Development Authority (BARDA).
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- 2023
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