Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial

Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week prim...

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Published in:	The lancet respiratory medicine 2022-11, Vol.10 (11), p.1049-1060
Main Authors:	Shaw, Robert H, Liu, Xinxue, Stuart, Arabella S V, Greenland, Melanie, Aley, Parvinder K, Andrews, Nick J, Cameron, J Claire, Charlton, Sue, Clutterbuck, Elizabeth A, Collins, Andrea M, Dejnirattisai, Wanwisa, Dinesh, Tanya, 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, Morey, Ella R, Provstgaard-Morys, Samuel, Ramasamy, Maheshi N, Ramsay, Mary, Read, Robert C, Robinson, Hannah, Screaton, Gavin R, Singh, Nisha, Turner, David P J, Turner, Paul J, Vichos, Iason, 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., Carson, Amy, Di Maso, Claudio, Mead, Gracie, Howe, Elizabeth G., 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., Crook, Rebecca, Bula, Marcin, Fyles, Fred, Burhan, Hassan, Maelin, Flora, Hughes, Elen, Okenyi, Emmanuel
Format:	Article
Language:	eng
Subjects:	Adult Antibodies, Viral BNT162 Vaccine ChAdOx1 nCoV-19 COVID-19 - prevention & control COVID-19 Vaccines - adverse effects Humans Immunization, Secondary Immunoglobulin G SARS-CoV-2
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Summary:	Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca). Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33). Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of sche
ISSN:	2213-2600 2213-2619