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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

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Title: 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
Authors: Shaw, RH
Liu, X
Stuart, ASV
Greenland, M
Aley, PK
Andrews, NJ
Cameron, JC
Charlton, S
Clutterbuck, EA
Collins, AM
Dejnirattisai, W
Dinesh, T
Faust, SN
Ferreira, DM
Finn, A
Green, CA
Hallis, B
Heath, PT
Hill, H
Lambe, T
Lazarus, R
Libri, V
Long, F
Mujadidi, YF
Plested, EL
Morey, ER
Provstgaard-Morys, S
Ramasamy, MN
Ramsay, M
Read, RC
Robinson, H
Screaton, GR
Singh, N
Turner, DPJ
Turner, PJ
Vichos, I
Walker, LL
White, R
Nguyen-Van-Tam, JS
Snape, MD
Com-COV Study Group
Item Type: Journal Article
Abstract: BACKGROUND: 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). METHODS: 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). FINDINGS: 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 schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19-BNT162b2 were up to 80% less reactogenic than 4-week schedules. INTERPRETATION: These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals. FUNDING: UK Vaccine Taskforce and National Institute for Health and Care Research.
Issue Date: 1-Nov-2022
Date of Acceptance: 14-Apr-2022
URI: http://hdl.handle.net/10044/1/97462
DOI: 10.1016/S2213-2600(22)00163-1
ISSN: 2213-2600
Publisher: Elsevier
Start Page: 1049
End Page: 1060
Journal / Book Title: The Lancet Respiratory Medicine
Volume: 10
Issue: 11
Copyright Statement: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Sponsor/Funder: National Institute for Health and Care Research
Funder's Grant Number: PR-R17-0916-22001/-02/-03/-04
Keywords: Adult
COVID-19 Vaccines
ChAdOx1 nCoV-19
BNT162 Vaccine
Immunization, Secondary
Antibodies, Viral
Immunoglobulin G
Com-COV Study Group
Immunoglobulin G
Antibodies, Viral
Immunization, Secondary
COVID-19 Vaccines
BNT162 Vaccine
ChAdOx1 nCoV-19
1103 Clinical Sciences
1117 Public Health and Health Services
1199 Other Medical and Health Sciences
Publication Status: Published
Conference Place: England
Online Publication Date: 2022-06-09
Appears in Collections:Department of Surgery and Cancer
National Heart and Lung Institute
Faculty of Medicine
Imperial College London COVID-19

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