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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 
ORCID: https://orcid.org/0000-0002-4094-1572, Dinesh, Tanya, England, Anna, Faust, Saul N, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902, 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 and Snape, Matthew D
(2021)
'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.'. Lancet, Vol 398, Issue 10303, pp. 856-869.
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Abstract
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.
| Item Type: | Article |
|---|---|
| Subjects: | QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58 Nucleic acids and derivatives (General) QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 505 Viral respiratory tract infections |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1016/S0140-6736(21)01694-9 |
| Depositing User: | Stacy Murtagh |
| Date Deposited: | 07 Oct 2021 12:33 |
| Last Modified: | 07 Oct 2021 12:33 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/18914 |
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