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

Lazarus, Rajeka; Baos, Sarah; Cappel-Porter, Heike; Carson‐Stevens, Andrew; Clout, Madeleine; Culliford, Lucy; Emmett, Stevan R.; Garstang, Joanna; Gbadamoshi, Lukuman; Hallis, Bassam; Harris, Rosie A; Hutton, David; Jacobsen, Nick; Joyce, Katherine; Kaminski, R.M.; Libri, Vincenzo; Middleditch, Alex; McCullagh, Liz; Moran, Ed; Phillipson, Adrian; Price, Elizabeth; Ryan, Kathryn A.; Thirard, Russell; Todd, Rachel; Snape, Matthew D; Tucker, David; Williams, R.; Nguyen‐Van‐Tam, Jonathan S; Finn, Adam; Rogers, Chris

doi:10.1016/s0140-6736(21)02329-1

Cited by 114 publications

(129 citation statements)

References 16 publications

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“…A 2021 study in the UK, involving 679 participants aged 18 years and older (randomly assigned to 12 study groups), showed that the coadministration of a second dose of the SARS-CoV-2 mRNA vaccine BNT162b2 (Pfizer-BioNTech) with one of three seasonal inactivated influenza vaccines had acceptable reactogenicity and tolerability, with no evidence of negative immune interference compared with administration of each vaccine alone. 46 Based on those preliminary data, the UK Government updated their guidance to support concomitant administration of the BNT162b2 vaccine with influenza vaccines (in separate arms) 47 and encouraged concomitant administration of the influenza vaccine with COVID-19 booster vaccination, where practical to do so. 34 An exploratory substudy of a phase 3 trial also reported no overall effect of coadministration of a first dose of COVID-19 protein-based vaccine NVX-CoV2373 coadministered with licensed seasonal quadrivalent (18–64 years old) or trivalent (≥65 years old) influenza vaccine on the safety and efficacy of either vaccine alone.…”

Section: Discussionmentioning

confidence: 99%

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

Izikson

Brune

Bolduc

et al. 2022

The Lancet Respiratory Medicine

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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...

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Section: Discussionmentioning

confidence: 99%

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

Izikson

Brune

Bolduc

et al. 2022

The Lancet Respiratory Medicine

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“…With regard to COVID-19/SIV vaccine co-administration, an increasing number of randomized controlled trials report data on non-clinically significant inferences (from the point of view of both safety and immunogenicity) of co-administering the available COVID-19 vaccines with age-appropriate SIVs. As of December 2021, these data are available for the cell-based, MF59-adjuvanted (when co-administered with ChAdOx1 [12], BNT162b2 [12] or NVX-CoV2373 [49]), recombinant (when co-administered with either ChAdOx1 or BNT162b2 [12]) and high-dose (when co-administered with mRNA-1273 [50]) SIVs. It is desirable that these co-administration data appear both in summaries of product characteristics (intended primarily for health professionals) and in package leaflets (intended primarily for patients) of both COVID-19 and influenza vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Preliminary data suggest that the concomitant administration of COVID-19 and SIV vaccines is a feasible option. Specifically, a recent phase IV randomized placebo-controlled trial [12] established that both ChAdOx1 and BNT162b2 COVID-19 vaccines could be safely co-administered with either MF59adjuvanted or cell-culture-derived SIVs, with no clinically significant increase in adverse events or immunologic inference. Although the available data are limited, the interim guidelines issued by the World Health Organization (WHO) [13] suggest that such coadministration is acceptable.…”

Section: Introductionmentioning

confidence: 99%

Acceptance of COVID-19 and Influenza Vaccine Co-Administration: Insights from a Representative Italian Survey

Domnich

Grassi²,

Fallani

et al. 2022

JPM

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Co-administration of coronavirus disease 2019 (COVID-19) and seasonal influenza vaccines has several advantages, has been advocated by various public health authorities and should be seen as an opportunity to increase the uptake of both vaccines. The objective of this survey was to quantify the acceptance of concomitant COVID-19/influenza vaccination and to identify its correlates in a representative sample of Italian adults. Of 2463 participants, a total of 22.9% were favorable to vaccine co-administration, while 16.6% declared their firm unwillingness to receive both vaccines simultaneously. The remaining 60.5% of subjects could be dubbed hesitant to some degree. Compliance with the primary COVID-19 vaccination schedule (adjusted proportional odds ratio (aOR) = 7.78), previous influenza vaccination (aOR = 1.89) and trust in public health institutions (aOR = 1.22) were the main determinants of positive attitudes toward vaccine co-administration. Other significant correlates included age, sex, perceived disease severity and vaccination risk–benefit, being offered a more personalized influenza vaccine and recent seeking for influenza-related information. In Italy, hesitancy toward COVID-19/influenza vaccine co-administration is common and appears to be higher than hesitancy toward either vaccine administered alone. This pattern is multifaceted and requires specific and tailored strategies, with public health institutions playing the central role.

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“…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. Three weeks later, those who had received placebo received SIV, and vice versa.…”

Section: Safety Immunogenicity and Efficacy Of Covid-19 And Influenza...mentioning

confidence: 99%

“…Indeed, apart from the statistical significance, geometric mean ratios of all pairwise comparisons have proved to be >0.67, which is the non-inferiority margin ( Table 2 ). Lazarus et al [ 40 ] did not observe any significant difference in geometric mean titers (GMTs) between most co-administration groups (ChAdOx1 + QIVc, ChAdOx1 + QIVr, ChAdOx1 + aTIV, BNT162b2 + QIVc or BNT162b2 + aTIV) and groups receiving SIVs alone. The only exception was the immune response to A(H1N1)pdm09, B/Victoria and B/Yamagata; in these cases, GMTs were 20–38% higher in the BNT162b2 + QIVr group than in individuals who received QIVr only.…”

Section: Safety Immunogenicity and Efficacy Of Covid-19 And Influenza...mentioning

confidence: 99%

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

et al. 2022

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SARS-CoV-2 and influenza are the main respiratory viruses for which effective vaccines are currently available. Strategies in which COVID-19 and influenza vaccines are administered simultaneously or combined into a single preparation are advantageous and may increase vaccination uptake. Here, we comprehensively review the available evidence on COVID-19/influenza vaccine co-administration and combination vaccine candidates from the standpoints of safety, immunogenicity, efficacy, policy and public acceptance. While several observational studies have shown that the trained immunity induced by influenza vaccines can protect against some COVID-19-related endpoints, it is not yet understood whether co-administration or combination vaccines can exert additive effects on relevant outcomes. In randomized controlled trials, co-administration has proved safe, with a reactogenicity profile similar to that of either vaccine administered alone. From the immunogenicity standpoint, the immune response towards four influenza strains and the SARS-CoV-2 spike protein in co-administration groups is generally non-inferior to that seen in groups receiving either vaccine alone. Several public health authorities have advocated co-administration. Different combination vaccine candidates are in (pre)-clinical development. The hesitancy towards vaccine co-administration or combination vaccines is a multifaceted phenomenon and may be higher than the acceptance of either vaccine administered separately. Public health implications are discussed.

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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

Cited by 114 publications

References 16 publications

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

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

Acceptance of COVID-19 and Influenza Vaccine Co-Administration: Insights from a Representative Italian Survey

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

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