Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Issue 10303 (4th September 2021)

• Record Type: Journal Article
• Authors: Liu, Xinxue; Shaw, Robert H; Stuart, Arabella S V; Greenland, Melanie; Aley, Parvinder K; Andrews, Nick J; Cameron, J Claire; Charlton, Sue; Clutterbuck, Elizabeth A; Collins, Andrea M; Dinesh, Tanya; England, Anna; Faust, Saul N; Ferreira, Daniela M; Finn, Adam; Green, Christopher A; Hallis, Bassam; Heath, Paul T; Hill, Helen; Lambe, Teresa; Lazarus, Rajeka; Libri, Vincenzo; Long, Fei; Mujadidi, Yama F; Plested, Emma L; Provstgaard-Morys, Samuel; Ramasamy, Maheshi N; Ramsay, Mary; Read, Robert C; Robinson, Hannah; Singh, Nisha; Turner, David P J; Turner, Paul J; Walker, Laura L; White, Rachel; Nguyen-Van-Tam, Jonathan S; Snape, Matthew D; Munro, Alasdair P S; Bartholomew, Jazz; Presland, Laura; Horswill, Sarah; Warren, Sarah; Varkonyi-Clifford, Sophie; Saich, Stephen; Adams, Kirsty; Ricamara, Marivic; Turner, Nicola; Yee Ting, Nicole Y; Whittley, Sarah; Rampling, Tommy; Desai, Amisha; Brown, Claire H; Qureshi, Ehsaan; Gokani, Karishma; Naker, Kush; Kellett Wright, Johanna K; Williams, Rachel L; Riaz, Tawassal; Penciu, Florentina D; Di Maso, Claudio; Howe, Elizabeth G; Vichos, Iason; Ghulam Farooq, Mujtaba; Noristani, Rabiullah; Yao, Xin L; Oldfield, Neil J; Hammersley, Daniel; Belton, Sue; Royal, Simon; San Francisco Ramos, Alberto; Hultin, Cecilia; Galiza, Eva P; Shiham, Farah; Solórzano, Carla; Sainsbury, Hannah; Davies, Kelly; Ambrose, Pauline; Hitchins, Lisa; Baker, Natalie; Leung, Stephanie; Fothergill, Ross; Godwin, Kerry; Buttigieg, Karen; Shaik, Imam; Brown, Phill; Knight, Chanice; Lall, Paminder; Allen, Lauren;
• Is Part Of: Lancet. Volume 398:Issue 10303(2021)
• Page Start: 856
• Page End: 869
• Publication Date: 2021-09-04
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Medicine; Electronic journals; Periodicals; 610.5
• DOI: 10.1016/S0140-6736(21)01694-9
• Languages: English
• ISSNs: 0140-6736

Abstract

Summary: Background: Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. Methods: Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139. Findings: Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation. Interpretation: Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. Funding: UK Vaccine Task Force and National Institute for Health Research.