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

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 (BNT...

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Published in:	The Lancet (British edition) 2021-09, Vol.398 (10303), p.856-869
Main 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
Format:	Article
Language:	eng
Subjects:	Adverse events Aged Antibodies, Viral - blood BNT162 Vaccine ChAdOx1 nCoV-19 Clinical trials Coronaviruses COVID-19 COVID-19 - prevention & control COVID-19 vaccines COVID-19 Vaccines - administration & dosage COVID-19 Vaccines - adverse effects COVID-19 Vaccines - immunology Enzyme-linked immunosorbent assay Equivalence Trials as Topic Evaluation Female Glycoproteins Homology Humans Immune response Immunization Immunization Schedule Immunogenicity Immunogenicity, Vaccine Immunoglobulin G Immunoglobulin G - blood Immunology Intention to Treat Analysis Intervals Laboratories Low income groups Male Middle Aged Minority & ethnic groups mRNA mRNA vaccines Safety Schedules Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Single-Blind Method Spike Glycoprotein, Coronavirus - immunology Vaccines Viral diseases
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Summary:	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. 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. 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-spi
ISSN:	0140-6736 1474-547X