Impact 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

File Description SizeFormat 
Com-COV Interval Paper - Revision Clean Main.docxFile embargoed for 6 months after publication date 507.95 kBMicrosoft Word    Request a copy
Com-COV Interval Paper - Revision Clean - Appendix.docxFile embargoed for 6 months after publication date 6.57 MBMicrosoft Word    Request a copy
Title: Impact 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, P
Vichos, J
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 may influence immune persistence and the relative importance of third-dose ‘booster’ programmes. Here, we report on the impact of 4- versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months following homologous and heterologous priming schedules using BNT162b2 (BNT, tozinameran, Comirnaty, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (ChAd, Vaxzevria, AstraZeneca). Methods: Com-COV is a participant-blinded, randomised immunogenicity trial. Results are reported here for the ‘General’ cohort, in which adults aged over 50 years were randomised to four homologous and heterologous schedules using BNT and ChAd with 4- or 12-week priming intervals. Immunogenicity analyses were on the intention-to-treat population (ITT), without evidence of COVID-19 infection at baseline or for the trial duration, with the purpose of describing the effect of priming interval on humoral and cellular immune response at peak and later timepoints, in addition to the effects on reactogenicity and safety Findings: Between 11th–26th Feb 2021, 730 participants were randomised in the general cohort, with 77-89 per arm in the ITT analysis. At 28-days and 6-months post-second dose, the geometric mean concentration (GMC) of anti-SARS-CoV-2 spike IgG was significantly higher in 12- versus 4-week interval arms for homologous schedules. In heterologous arms, there was only a significant difference between intervals for the BNT/ChAd arm at 28-days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week versus 4-week schedules, 28-days post-second dose, with geometric mean ratios 1.4 (95%CI: 1.1-1.8, BNT/BNT), 1.5 (95%CI: 1.2-1.9, ChAd/BNT), 1.6 (95%CI 1.3-2.1, BNT/ChAd) and2.4 (95%CI: 1.7-3.2, ChAd/ChAd). At 6 months post-second dose, anti-spike IgG GMCs fell to 0.17-0.24 of the 28-day post-second dose value across all eight study arms, with only BNT/BNT displaying a slightly slower decay for the 12-week versus 4-week schedule in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval with BNT/BNT remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals versus their 4-week counterparts. 12-week schedules for BNT/BNT and ChAd/BNT schedules 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 may result in lower reactogenicity in schedules with BNT as a second-dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines employing these novel platforms may benefit from prolonged-interval schedules. ISRCTN:69254139, EudraCT:2020-005085-33.
Date of Acceptance: 27-Apr-2022
ISSN: 2213-2600
Publisher: Elsevier
Journal / Book Title: The Lancet Respiratory Medicine
Sponsor/Funder: National Institute for Health and Care Research
Funder's Grant Number: PR-R17-0916-22001/-02/-03/-04
Keywords: 1103 Clinical Sciences
1117 Public Health and Health Services
1199 Other Medical and Health Sciences
Publication Status: Accepted
Embargo Date: Embargoed for 6 months after publication date
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine
Imperial College London COVID-19

Unless otherwise indicated, items in Spiral are protected by copyright and are licensed under a Creative Commons Attribution NonCommercial NoDerivatives License.

Creative Commons