Safety and immunogenicity of a SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in healthy adults: interim findings from a phase 2, randomised, dose-finding, multi-centre study
Authors: Sridhar Saranya , Joaquin Arnel , Bonaparte Matthew I , Bueso Agustin , Chabanon Anne-Laure , Chen Aiying , Chicz Roman M. , Diemert David , Essink Brandon J , Fu Bo , Grunenberg Nicole A , Janosczyk Helene , Keefer Michael C , Rivera M Doris M , Meng Ya , Michael Nelson L. , Munsiff Sonal S , Ogbuagu Onyema , Raabe Vanessa N , Severance Randall , Rivas Enrique , Romanyak Natalya , Rouphael Nadine G , Schuerman Lode , Sher Lawrence D , Walsh Stephen R , White Judith , von Barbier Dalia , de Bruyn Guy , Canter Richard , Grillet Marie-Helene , Keshtkar-Jahromi Maryam , Koutsoukos Marguerite , Lopez Denise , Masotti Roger , Mendoza Sandra , Moreau Catherine , Ceregido Maria Angeles , Ramirez Shelly , Said Ansoyta , Tavares-Da-Silva Fernanda , Shi Jiayuan , Tong Tina , Treanor John , Diazgranados Carlos A , Savarino Stephen 
Published: October 2021

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 5μg, 10μg or 15μg 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 (5μg, n=240; 10μg, n=239; 15μg, 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 naïve participants at D36, 96·9%, 97.0% and 97·6% of participants had ≥4-fold-rise in NAb titres from baseline in the 5μg-, 10μg- and 15μg-dose groups, respectively. NAb titres increased with antigen dose in younger (GMTs: 2954, 3951 and 5142 for 5μg-, 10μg- and 15μg-dose groups) but not older adults (GMTs: 1628, 1393 and 1736, respectively). NAb titres in non-naïve adults after one injection were higher than titres after two injections in naïve adults.

Interpretation

Two injections of CoV2 preS dTM-AS03 demonstrated acceptable safety and reactogenicity, and robust immunogenicity in SARS-CoV-2 naïve and non-naïve adults. These results informed antigen dose selection for progression to Phase 3 evaluation of primary and booster vaccination.