학술논문
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
Document Type
article
Author
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; Yvonne Davis
Source
EClinicalMedicine, Vol 62, Iss , Pp 102109- (2023)
Subject
Language
English
ISSN
2589-5370
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).