Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial

ComfluCOV Trial Group

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Abstract

Background: Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine. Methods: In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248. Findings: Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebos −1·29%, 95% CI −14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, −6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (–12·9%, −34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, −13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, −5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, −11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. Interpretation: Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need. Funding: National Institute for Health Research Policy Research Programme

Original languageEnglish
Pages (from-to)2277-2287
Number of pages11
JournalThe Lancet
Volume398
Issue number10318
DOIs
Publication statusPublished - 18 Dec 2021

Bibliographical note

Funding Information:
We would like to thank all the trial participants, without whom this trial would not have been possible. We thank all site staff involved in recruitment, coordination, and data collection for this trial. We also thank the clinical, nursing, vaccination, and administrative teams at participating centres for their support in the conduct of the trial. We would like to acknowledge the contribution of the Oxford Vaccine Group to the trial and documentation design. We would like to acknowledge the Data Monitoring and Safety Committee (DMSC) and Trial Steering Committee (TSC) for their support and oversight of the trial. The independent DMSC members are: David Lewis (Chair), Krishnan Bhaskaran, Judith Breuer, Stephen JW Evans, Ian M Feavers, Hanna Nohynek, Mark Toshner, and Paul Moss. The independent TSC members are Robert Read (Chair), Mary Ramsay, Claire Cameron, and Paul J Turner. Nick Andrews is a non-independent member of the TSC. We would like to thank the sponsor organisation, University Hospitals Bristol and Weston NHS Foundation Trust, and the National Immunisation Schedule Evaluation Consortium. This trial was funded by the National Institute for Health Research Policy Research Programme (PR-R17-0916-22001, NIHR203243). The views in this Article are those of the authors and not necessarily those of the UK Department of Health and Social Care.

Funding Information:
RL reports grants from the National Institute for Health Research (NIHR) during the conduct of the trial, and grants from Elizabeth Blackwell Institute, AstraZeneca, Janssen, and Valneva outside the submitted work. CAR reports grants from NIHR, during the conduct of the trial. JSN-V-T reports that he is seconded to the Department of Health and Social Care, England. AF reports grants from Pfizer during the conduct of the trial, and grants from Elizabeth Blackwell Institute, Sanofi Pasteur, VBI Vaccines, Pfizer, Janssen, GSK, MedImmune, Novavax, and Valneva outside the submitted work. AM reports grants from NIHR during the conduct of the trial, and grants from AstraZeneca, Janssen, and Valneva outside the submitted work. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers, including AstraZeneca, GSK, Pfizer, Novavax, Pfizer, Janssen, Medimmune, and MCM. All other authors declare no competing interests.

Funding Information:
We would like to thank all the trial participants, without whom this trial would not have been possible. We thank all site staff involved in recruitment, coordination, and data collection for this trial. We also thank the clinical, nursing, vaccination, and administrative teams at participating centres for their support in the conduct of the trial. We would like to acknowledge the contribution of the Oxford Vaccine Group to the trial and documentation design. We would like to acknowledge the Data Monitoring and Safety Committee (DMSC) and Trial Steering Committee (TSC) for their support and oversight of the trial. The independent DMSC members are: David Lewis (Chair), Krishnan Bhaskaran, Judith Breuer, Stephen JW Evans, Ian M Feavers, Hanna Nohynek, Mark Toshner, and Paul Moss. The independent TSC members are Robert Read (Chair), Mary Ramsay, Claire Cameron, and Paul J Turner. Nick Andrews is a non-independent member of the TSC. We would like to thank the sponsor organisation, University Hospitals Bristol and Weston NHS Foundation Trust, and the National Immunisation Schedule Evaluation Consortium. This trial was funded by the National Institute for Health Research Policy Research Programme (PR-R17-0916-22001, NIHR203243). The views in this Article are those of the authors and not necessarily those of the UK Department of Health and Social Care.

Publisher Copyright:
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

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