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