ABSTRACT
Background This study evaluated the safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein candidate vaccine, CoV2 preS dTM. Methods This Phase 2, modified double-blind, parallel-group study (NCT04762680) was conducted in adults, including those at increased risk of severe COVID-19. Participants were randomised 1:1:1, stratified by age (18-59/[≥]60 years), rapid serodiagnostic test (positive/negative) and high-risk medical conditions (yes/no), to receive two injections (day [D]1 and D22) of 5{micro}g, 10{micro}g or 15{micro}g of CoV2 preS dTM antigen with fixed AS03 content. Interim safety and reactogenicity results (to D43) and neutralising antibodies (Nabs) against the D614G variant are presented (primary objectives). Findings Of 722 participants enrolled and randomised between 24 February and 8 March 2021, 721 received [≥]1 injections (5{micro}g, n=240; 10{micro}g, n=239; 15{micro}g, n=242). Four participants reported unsolicited immediate adverse events (AEs), two were vaccine-related (investigator assessment). Five participants reported seven vaccine-related medically-attended AEs. No vaccine-related serious AEs and no AEs of special interest were reported. Solicited reactions (local and systemic) were reported at similar frequencies between study groups; these were mostly mild to moderate and transient, with higher frequency and intensity post-injection 2 than post-injection 1. In SARS-CoV-2 na ive participants at D36, 96'9%, 97.0% and 97'6% of participants had [≥]4-fold-rise in NAb titres from baseline in the 5{micro}g-, 10{micro}g- and 15{micro}g-dose groups, respectively. NAb titres increased with antigen dose in younger (GMTs: 2954, 3951 and 5142 for 5{micro}g-, 10{micro}g- and 15{micro}g-dose groups) but not older adults (GMTs: 1628, 1393 and 1736, respectively). NAb titres in non-na ive adults after one injection were higher than titres after two injections in na ive adults. Interpretation Two injections of CoV2 preS dTM-AS03 demonstrated acceptable safety and reactogenicity, and robust immunogenicity in SARS-CoV-2 na ive and non-na ive adults. These results informed antigen dose selection for progression to Phase 3 evaluation of primary and booster vaccination.