Tags

Type your tag names separated by a space and hit enter

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.
Lancet Respir Med. 2022 11; 10(11):1049-1060.LR

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.

Authors+Show Affiliations

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Department of Infection, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: robert.shaw@paediatrics.ox.ac.uk.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Department of Infection, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, UK; 3Statistics, Modelling and Economics Department, UK Health Security Agency, London, UK.Public Health Scotland, Glasgow-Edinburgh, Scotland, UK.UK Health Security Agency, Porton Down, Salisbury, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Liverpool Vaccine Group, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.Liverpool Vaccine Group, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.Bristol Vaccine Centre, Schools of Population Health Sciences and Cellular and Molecular Medicine, University of Bristol, Bristol, UK.NIHR-Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.UK Health Security Agency, Porton Down, Salisbury, UK.The Vaccine Institute, St George's University of London, London, UK.Liverpool Vaccine Group, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK.North Bristol NHS Trust, Bristol, UK.NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Department of Infection, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, UK.NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.School of Life Sciences, University of Nottingham, and Department of Microbiology, Nottingham University Hospitals NHS Trust, Nottingham, UK.National Heart & Lung Institute, Imperial College London, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford NIHR-Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.No affiliation info available

Pub Type(s)

Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35690076

Citation

Shaw, Robert H., et al. "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." The Lancet. Respiratory Medicine, vol. 10, no. 11, 2022, pp. 1049-1060.
Shaw RH, Liu X, Stuart ASV, et al. 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. Lancet Respir Med. 2022;10(11):1049-1060.
Shaw, R. H., Liu, X., Stuart, A. S. V., Greenland, M., Aley, P. K., Andrews, N. J., Cameron, J. C., Charlton, S., Clutterbuck, E. A., Collins, A. M., Dejnirattisai, W., Dinesh, T., Faust, S. N., Ferreira, D. M., Finn, A., Green, C. A., Hallis, B., Heath, P. T., Hill, H., ... Snape, M. D. (2022). 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. The Lancet. Respiratory Medicine, 10(11), 1049-1060. https://doi.org/10.1016/S2213-2600(22)00163-1
Shaw RH, et al. 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. Lancet Respir Med. 2022;10(11):1049-1060. PubMed PMID: 35690076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Shaw,Robert H, AU - Liu,Xinxue, AU - Stuart,Arabella S V, AU - Greenland,Melanie, AU - Aley,Parvinder K, AU - Andrews,Nick J, AU - Cameron,J Claire, AU - Charlton,Sue, AU - Clutterbuck,Elizabeth A, AU - Collins,Andrea M, AU - Dejnirattisai,Wanwisa, AU - Dinesh,Tanya, AU - Faust,Saul N, AU - Ferreira,Daniela M, AU - Finn,Adam, AU - Green,Christopher A, AU - Hallis,Bassam, AU - Heath,Paul T, AU - Hill,Helen, AU - Lambe,Teresa, AU - Lazarus,Rajeka, AU - Libri,Vincenzo, AU - Long,Fei, AU - Mujadidi,Yama F, AU - Plested,Emma L, AU - Morey,Ella R, AU - Provstgaard-Morys,Samuel, AU - Ramasamy,Maheshi N, AU - Ramsay,Mary, AU - Read,Robert C, AU - Robinson,Hannah, AU - Screaton,Gavin R, AU - Singh,Nisha, AU - Turner,David P J, AU - Turner,Paul J, AU - Vichos,Iason, AU - Walker,Laura L, AU - White,Rachel, AU - Nguyen-Van-Tam,Jonathan S, AU - Snape,Matthew D, AU - ,, Y1 - 2022/06/09/ PY - 2022/03/09/received PY - 2022/04/04/revised PY - 2022/04/14/accepted PY - 2022/6/12/pubmed PY - 2022/11/9/medline PY - 2022/6/11/entrez SP - 1049 EP - 1060 JF - The Lancet. Respiratory medicine JO - Lancet Respir Med VL - 10 IS - 11 N2 - 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. SN - 2213-2619 UR - https://www.unboundmedicine.com/medline/citation/35690076/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_ DB - PRIME DP - Unbound Medicine ER -