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 aged ≥65 years: a phase 2, randomised, open-label study

Abstract

Background Concomitant 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 aimed to assess 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. Methods This study is an ongoing, phase 2, multicentre, open-label, descriptive trial at six clinical research sites in the USA. We describe the interim results up to 21 days after vaccination (July–August, 2021). Community-dwelling adults aged 65 years and older, who were previously vaccinated with a two-dose primary schedule of the mRNA-1273 SARS-CoV-2 vaccine, were eligible for inclusion. The second dose of the primary mRNA-1273 vaccination series was required to have been received at least 5 months before enrolment in the study. Participants were randomly assigned (1:1:1) using a permuted block method stratified by site and by age group (<75 years vs ≥75 years), to receive concomitant administration of QIV-HD and mRNA-1273 vaccine, QIV-HD alone, or mRNA-1273 vaccine alone. Randomisation lists, generated by Sanofi Pasteur biostatistics platform, were provided to study investigators for study group allocation. Unsolicited adverse events occurring immediately, solicited local and systemic reactions up to day 8, and unsolicited adverse events, serious adverse events, adverse events of special interest, and medically attended adverse events up to day 22 were reported. Haemagglutination inhibition 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 day 1 and day 22. All analyses were descriptive. The study is registered with ClinicalTrials.gov , NCT04969276 . Findings Between July 16 and Aug 31, 2021, 306 participants were enrolled and randomly assigned, of whom 296 received at least one vaccine dose (100 in the coadministration group, 92 in the QIV-HD, and 104 in the mRNA-1273 group). Reactogenicity profiles were similar between the coadministration and mRNA-1273 groups, with lower reactogenicity rates in the QIV-HD group (frequency of solicited injection site reactions 86·0% [95% CI 77·6–92·1], 91·3% [84·2–96·0], and 61·8% [50·9–71·9]; frequency of solicited systemic reactions 80·0%, [70·8–87·3], 83·7% [75·1–90·2], and 49·4% [38·7–60·2], respectively). Up to day 22, unsolicited adverse events were reported for 17·0% (95% CI 10·2–25·8) of participants in the coadministration group and 14·4% (8·3–22·7) of participants in the mRNA-1273 group, and tended to be reported at a slightly lower rate (10·9% [5·3–19·1]) in participants in the QIV-HD group. Seven participants e...

COVID-19 and Seasonal Influenza Vaccination: Cross-Protection, Co-Administration, Combination Vaccines, and Hesitancy

“…As of February 2022, three randomized controlled trials (RCTs) [ 40 , 41 , 42 ] on COVID-19 and SIV vaccine co-administration are available. In a phase IV trial conducted in the United Kingdom (UK) [ 40 ], adults were randomized (1:1; n = 679) to receive either a second dose of ChAdOx1 (Vaxzevria, AstraZeneca, Cambridge, UK) or BNT162b2 vaccines, together with an age-appropriate SIV (QIVc, recombinant quadrivalent influenza vaccine (QIVr; Supemtek, Sanofi Pasteur, Lyon, France) for subjects aged 18–64 years and MF59-adjuvanted trivalent influenza vaccine (aTIV; Fluad, Seqirus) for those aged ≥65 years) or ChAdOx1/BNT162b2 together with placebo.…”

“…Toback et al [ 41 ] reported the results of a phase III efficacy RCT, in which a subset of adults was randomized (1:1; n = 431) to receive the first dose of NVX-CoV2373 (Nuvaxovid, Novavax CZ a.s., Jevany, Czech Republic) plus SIV (QIVc and aTIV for subjects aged 18–64 and ≥65 years, respectively) or SIV alone. Finally, the interim results of a phase II RCT have recently been reported [ 42 ]; in this trial, elderly individuals (≥65 years) were randomized (1:1:1; n = 431) to receive a second dose of mRNA-1273 (Spikevax, Moderna, Cambridge, MA, USA) plus a high-dose quadrivalent influenza vaccine (hdQIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur, Lyon, France), a dose of hdQIV alone or a second dose of mRNA-1273 alone. In all three RCTs [ 41 , 42 ], vaccines were co-administered in opposite arms in each subject.…”

“…Finally, the interim results of a phase II RCT have recently been reported [ 42 ]; in this trial, elderly individuals (≥65 years) were randomized (1:1:1; n = 431) to receive a second dose of mRNA-1273 (Spikevax, Moderna, Cambridge, MA, USA) plus a high-dose quadrivalent influenza vaccine (hdQIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur, Lyon, France), a dose of hdQIV alone or a second dose of mRNA-1273 alone. In all three RCTs [ 41 , 42 ], vaccines were co-administered in opposite arms in each subject.…”

“…All three RCTs [ 41 , 42 ] reported no major safety concerns regarding COVID-19 + SIV co-administration. Specifically, as reported in Table 1 , the overall rate of solicited local (especially pain in the injection site) and systemic adverse events was similar between subjects who received COVID-19 + SIV and those who received the COVID-19 vaccine alone.…”

“…Toback et al [ 41 ] did not find any significant difference in HAI titers between COVID-19 + SIV and placebo + SIV groups, regardless of the strain or vaccine (QIVc or aTIV). Analogously, the humoral immune response towards all four SIV strains was similar in individuals who received mRNA-1273 + hdQIV or hdQIV alone [ 42 ].…”