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

BackgroundBooster vaccines providing protection against emergent SARS-CoV-2 variants are needed. In an international phase 3 study, we evaluated booster vaccines containing prototype (D614) and/or Beta (B.1.351) variant recombinant spike proteins and AS03 adjuvant (CoV2 preS dTM-AS03). MethodsAdults, primed 4-10 months earlier with mRNA (BNT162b2, mRNA-1273]), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or adjuvanted protein (CoV2 preS dTM-AS03 [D614]) vaccines and stratified by age (18-55 and [≥]56 years), were boosted with monovalent (MV) D614 (5g, n=1285), MV (B.1351) (5g, n=707) or bivalent (BiV) (2.5g D614 plus 2.5g B.1.351, n=625) CoV2 preS dTM-AS03. SARS-CoV-2-naive adults (controls, n=479) received a primary series (two injections, 21 days apart) of CoV2 preS dTM-AS03 containing 10g D614. Antibodies to D614G, B.1.351 and Omicron BA.2 and BA.1 variants were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay. D614G or B.1.351 PsVN titers 14 days (D15) post-booster were compared with pre-booster (D1) titers in BNT162b2-primed participants (18-55 years old) and controls (D36), for each booster formulation (co-primary objectives). Safety was evaluated throughout the trial. Results of a planned interim analysis are presented. ResultsAmong BNT162b2-primed adults (18-55 years old), PsVN titers against D614G or B.1.351 were significantly higher post-booster than anti-D614G titers post-primary vaccination in controls, for all booster formulations, with an anti-D614G GMT ratio (98.3% CI) of 2.16 (1.69; 2.75) for MV(D614), an anti-B.1.351 ratio of 1.96 (1.54; 2.50) for MV (B.1.351) and anti-D614G and anti-B.1.351 ratios of 2.34 (1.84; 2.96) and 1.39 (1.09; 1.77), respectively, for BiV. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 across vaccine priming subgroups and against Omicron BA.1 (evaluated in BNT162b2-primed participants). Similar patterns in antibody responses were observed for participants aged [≥]56 years. No safety concerns were identified. ConclusionCoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. ClinicalTrials.govNCT04762680 FundingSanofi and federal funds from the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Administration for Strategic Preparedness and Response at the U.S. Department of Health and Human Services under Contract # HHSO100201600005I, and in collaboration with the U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense under Contract # W15QKN-16-9-1002.

Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults >= 65 years of age: a Phase II, open-label study

BackgroundConcomitant seasonal influenza vaccination with a COVID-19 vaccine booster could help to minimise potential disruption to the seasonal influenza vaccination campaign and maximise protection against both diseases among individuals at risk of severe disease and hospitalisation. This study assesses the safety and immunogenicity of concomitant administration of high-dose quadrivalent influenza vaccine (QIV-HD) and a mRNA-1273 vaccine booster dose in older adults. MethodsThis is an ongoing Phase II, multi-centre, open-label study (NCT04969276). We describe interim results up to 21 days after vaccination (July 2021-August 2021). Adults aged [≥] 65 years living in the community, who were to have received a second mRNA-1273 dose at least five months previously, were randomised (1:1:1) to concomitant QIV-HD and mRNA-1273 vaccination (Coad), QIV-HD alone, or mRNA-1273 vaccine alone. Unsolicited adverse events (AEs) occurring immediately, solicited local and systemic reactions up to day (D)8, and unsolicited AEs, serious AEs (SAEs), AEs of special interest (AESIs) and medically attended AEs (MAAEs) up to D22 were reported. Haemagglutination inhibition (HAI) antibody responses to influenza A/H1N1, A/H3N2, B/Yamagata and B/Victoria strains and SARS CoV-2 binding antibody responses (SARS-CoV-2 Pre-Spike IgG ELISA) were assessed at D1 and D22. FindingsOf 306 participants randomised, 296 were included for analysis (Coad, n=100; QIV-HD, n=92; mRNA-1273, n=104). Reactogenicity profiles were similar between the Coad and mRNA-1273 groups, with lower reactogenicity rates in the QIV-HD group (frequency [95% CIs] of solicited injection site reactions: 86{middle dot}0% [77{middle dot}6-92{middle dot}1], 91{middle dot}3% [84{middle dot}2-96{middle dot}0] and 61{middle dot}8% [50{middle dot}9-71{middle dot}9]; solicited systemic reactions: 80{middle dot}0% [70{middle dot}8-87{middle dot}3], 83{middle dot}7% [75{middle dot}1-90{middle dot}2] and 49{middle dot}4% [38{middle dot}7-60{middle dot}2], respectively). Up to D22, unsolicited AEs were reported for 17{middle dot}0% and 14{middle dot}4% participants in the Coad and mRNA-1273 groups, respectively, with a lower rate (10{middle dot}9%) in the QIV-HD group. Seven MAAEs were reported (Coad, n=3; QIV-HD, n=1; mRNA-1273, n=3). There were no SAEs, AESIs or deaths. HAI antibody geometric mean titres (GMTs) increased from D1 to D22 to similar levels for each influenza strain in the Coad and QIV-HD groups (GMTs [95% confidence interval], range across strains: Coad, 286 [233-352] to 429 [350-525]; QIV-HD, 315 [257-386] to 471 [378-588]). SARS-CoV-2 binding antibody geometric mean concentrations (GMCs) also increased to similar levels in the Coad and mRNA-1273 groups (D22 GMCs [95% confidence interval]: 7634 [6445-9042] and 7904 [6883- 9077], respectively). InterpretationNo safety concerns or immune interference were observed for concomitant administration of QIV-HD with mRNA-1273 booster in adults aged [≥] 65 years, supporting co-administration recommendations. FundingSanofi Pasteur