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Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.
J Infect. 2022 06; 84(6):795-813.JI

Abstract

OBJECTIVES

To evaluate the persistence of immunogenicity three months after third dose boosters.

METHODS

COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.

RESULTS

Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.

CONCLUSIONS

84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

Authors+Show Affiliations

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. Electronic address: xinxue.liu@paediatrics.ox.ac.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.Imperial Clinical Trials Unit, Imperial College London, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.Stockport NHS Foundation Trust, Stockport, UK.NIHR Liverpool and Broadgreen Clinical Research Facility, Liverpool, 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.NIHR Cambridge Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.NIHR Liverpool and Broadgreen Clinical Research Facility, Liverpool, UK.PHARMExcel. Welwyn Garden City, Hertfordshire, UK.NIHR/Wellcome Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK; MRC Clinical Trials Unit, University College London, London, UK.NIHR/Wellcome Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.Portsmouth Hospitals University NHS Trust, Portsmouth, UK.Queen Elizabeth University Hospital, NHS Greater Glasgow & Clyde, Glasgow, UK.Portsmouth Hospitals University NHS Trust, Portsmouth, UK.Wellcome-MRC Institute of Metabolic Science, Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.Cancer Research UK Oxford Centre, University of Oxford, Oxford, UK.NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.University Hospitals Sussex NHS Foundation Trust, Brighton, UK.Department of Infectious Diseases and Tropical Medicine, London Northwest University Healthcare, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.The Adam Practice, Poole, UK.Stockport NHS Foundation Trust, Stockport, UK.NIHR Oxford Biomedical Research Centre, Oxford, UK.NIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, UK.Public Health Wales, Betsi Cadwaladr University Health Board, Bangor University, Bangor, UK.University of Liverpool, Liverpool, 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.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.University Hospitals of Leicester NHS Trust, University of Leicester, Leicester, UK.University Hospitals of Leicester NHS Trust, University of Leicester, Leicester, UK.NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.Bradford Institute for Health Research and Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK.Bradford Institute for Health Research and Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.University Hospitals Sussex NHS Foundation Trust, Brighton, UK.Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.Department of Infectious Diseases and Tropical Medicine, London Northwest University Healthcare, London, UK.Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Queen Elizabeth University Hospital, NHS Greater Glasgow & Clyde, Glasgow, UK; MRC University of Glasgow Centre for Virus Research, Glasgow, UK.Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.NIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, 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.UK Health Security Agency, Porton Down, UK.UK Health Security Agency, Porton Down, UK.UK Health Security Agency, Colindale, London, UK.UK Health Security Agency, Colindale, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Division of Epidemiology and Public Health, University of Nottingham School of Medicine.Imperial Clinical Trials Unit, Imperial College London, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, 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. Electronic address: s.faust@soton.ac.uk.No affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35405168

Citation

Liu, Xinxue, et al. "Persistence of Immunogenicity After Seven COVID-19 Vaccines Given as Third Dose Boosters Following Two Doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three Month Analyses of the COV-BOOST Trial." The Journal of Infection, vol. 84, no. 6, 2022, pp. 795-813.
Liu X, Munro APS, Feng S, et al. Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial. J Infect. 2022;84(6):795-813.
Liu, X., Munro, A. P. S., Feng, S., Janani, L., Aley, P. K., Babbage, G., Baxter, D., Bula, M., Cathie, K., Chatterjee, K., Dejnirattisai, W., Dodd, K., Enever, Y., Qureshi, E., Goodman, A. L., Green, C. A., Harndahl, L., Haughney, J., Hicks, A., ... Faust, S. N. (2022). Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial. The Journal of Infection, 84(6), 795-813. https://doi.org/10.1016/j.jinf.2022.04.018
Liu X, et al. Persistence of Immunogenicity After Seven COVID-19 Vaccines Given as Third Dose Boosters Following Two Doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three Month Analyses of the COV-BOOST Trial. J Infect. 2022;84(6):795-813. PubMed PMID: 35405168.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial. AU - Liu,Xinxue, AU - Munro,Alasdair P S, AU - Feng,Shuo, AU - Janani,Leila, AU - Aley,Parvinder K, AU - Babbage,Gavin, AU - Baxter,David, AU - Bula,Marcin, AU - Cathie,Katrina, AU - Chatterjee,Krishna, AU - Dejnirattisai,Wanwisa, AU - Dodd,Kate, AU - Enever,Yvanne, AU - Qureshi,Ehsaan, AU - Goodman,Anna L, AU - Green,Christopher A, AU - Harndahl,Linda, AU - Haughney,John, AU - Hicks,Alexander, AU - van der Klaauw,Agatha A, AU - Kwok,Jonathan, AU - Libri,Vincenzo, AU - Llewelyn,Martin J, AU - McGregor,Alastair C, AU - Minassian,Angela M, AU - Moore,Patrick, AU - Mughal,Mehmood, AU - Mujadidi,Yama F, AU - Holliday,Kyra, AU - Osanlou,Orod, AU - Osanlou,Rostam, AU - Owens,Daniel R, AU - Pacurar,Mihaela, AU - Palfreeman,Adrian, AU - Pan,Daniel, AU - Rampling,Tommy, AU - Regan,Karen, AU - Saich,Stephen, AU - Serafimova,Teona, AU - Saralaya,Dinesh, AU - Screaton,Gavin R, AU - Sharma,Sunil, AU - Sheridan,Ray, AU - Sturdy,Ann, AU - Supasa,Piyada, AU - Thomson,Emma C, AU - Todd,Shirley, AU - Twelves,Chris, AU - Read,Robert C, AU - Charlton,Sue, AU - Hallis,Bassam, AU - Ramsay,Mary, AU - Andrews,Nick, AU - Lambe,Teresa, AU - Nguyen-Van-Tam,Jonathan S, AU - Cornelius,Victoria, AU - Snape,Matthew D, AU - Faust,Saul N, AU - ,, Y1 - 2022/04/09/ PY - 2022/03/17/received PY - 2022/04/04/revised PY - 2022/04/05/accepted PY - 2022/4/12/pubmed PY - 2022/5/26/medline PY - 2022/4/11/entrez KW - COVID-19 vaccine KW - Fractional dose KW - Heterologous boost KW - Homologous boost KW - Immunogenicity KW - Persistence KW - Third dose SP - 795 EP - 813 JF - The Journal of infection JO - J Infect VL - 84 IS - 6 N2 - OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses. SN - 1532-2742 UR - https://www.unboundmedicine.com/medline/citation/35405168/Persistence_of_immunogenicity_after_seven_COVID_19_vaccines_given_as_third_dose_boosters_following_two_doses_of_ChAdOx1_nCov_19_or_BNT162b2_in_the_UK:_Three_month_analyses_of_the_COV_BOOST_trial_ DB - PRIME DP - Unbound Medicine ER -