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

Xinxue Liu; Alasdair P S Munro; Shuo Feng; Leila Janani; Parvinder K Aley; Gavin Babbage; David Baxter; Marcin Bula; Katrina Cathie; Krishna Chatterjee; Wanwisa Dejnirattisai; Kate Dodd; Yvanne Enever; Ehsaan Qureshi; Anna L Goodman; Christopher A Green; Linda Harndahl; John Haughney; Alexander Hicks; Agatha A van der Klaauw; Jonathan Kwok; Vincenzo Libri; Martin J Llewelyn; Alastair C McGregor; Angela M Minassian; Patrick Moore; Mehmood Mughal; Yama F Mujadidi; Kyra Holliday; Orod Osanlou; Rostam Osanlou; Daniel R Owens; Mihaela Pacurar; Adrian Palfreeman; Daniel Pan; Tommy Rampling; Karen Regan; Stephen Saich; Teona Serafimova; Dinesh Saralaya; Gavin R Screaton; Sunil Sharma; Ray Sheridan; Ann Sturdy; Piyada Supasa; Emma C Thomson; Shirley Todd; Chris Twelves; Robert C Read; Sue Charlton; Bassam Hallis; Mary Ramsay; Nick Andrews; Teresa Lambe; Jonathan S Nguyen-Van-Tam; Victoria Cornelius; Matthew D Snape; Saul N Faust; COV-BOOST study group

doi:10.1016/j.jinf.2022.04.018

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 Jun;84(6):795-813. doi: 10.1016/j.jinf.2022.04.018. Epub 2022 Apr 9.

Authors

Xinxue Liu¹, Alasdair P S Munro², Shuo Feng³, Leila Janani⁴, Parvinder K Aley⁵, Gavin Babbage⁶, David Baxter⁷, Marcin Bula⁸, Katrina Cathie², Krishna Chatterjee⁹, Wanwisa Dejnirattisai¹⁰, Kate Dodd⁸, Yvanne Enever¹¹, Ehsaan Qureshi¹², Anna L Goodman¹³, Christopher A Green¹², Linda Harndahl¹⁴, John Haughney¹⁵, Alexander Hicks¹⁴, Agatha A van der Klaauw¹⁶, Jonathan Kwok¹⁷, Vincenzo Libri¹⁸, Martin J Llewelyn¹⁹, Alastair C McGregor²⁰, Angela M Minassian²¹, Patrick Moore²², Mehmood Mughal⁷, Yama F Mujadidi²³, Kyra Holliday²⁴, Orod Osanlou²⁵, Rostam Osanlou²⁶, Daniel R Owens², Mihaela Pacurar², Adrian Palfreeman²⁷, Daniel Pan²⁷, Tommy Rampling¹⁸, Karen Regan²⁸, Stephen Saich⁶, Teona Serafimova²⁹, Dinesh Saralaya²⁸, Gavin R Screaton¹⁰, Sunil Sharma¹⁹, Ray Sheridan³⁰, Ann Sturdy²⁰, Piyada Supasa¹⁰, Emma C Thomson³¹, Shirley Todd³⁰, Chris Twelves²⁴, Robert C Read², Sue Charlton³², Bassam Hallis³², Mary Ramsay³³, Nick Andrews³³, Teresa Lambe³, Jonathan S Nguyen-Van-Tam³⁴, Victoria Cornelius⁴, Matthew D Snape⁵, Saul N Faust³⁵; COV-BOOST study group

Affiliations

¹ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. Electronic address: [email protected].
² 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.
³ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
⁴ Imperial Clinical Trials Unit, Imperial College London, London, UK.
⁵ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
⁶ NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ Stockport NHS Foundation Trust, Stockport, UK.
⁸ NIHR Liverpool and Broadgreen Clinical Research Facility, Liverpool, UK.
⁹ NIHR Cambridge Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹⁰ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹¹ PHARMExcel. Welwyn Garden City, Hertfordshire, UK.
¹² NIHR/Wellcome Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹³ Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK; MRC Clinical Trials Unit, University College London, London, UK.
¹⁴ Portsmouth Hospitals University NHS Trust, Portsmouth, UK.
¹⁵ Queen Elizabeth University Hospital, NHS Greater Glasgow & Clyde, Glasgow, UK.
¹⁶ Wellcome-MRC Institute of Metabolic Science, Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.
¹⁷ Cancer Research UK Oxford Centre, University of Oxford, Oxford, UK.
¹⁸ NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
¹⁹ University Hospitals Sussex NHS Foundation Trust, Brighton, UK.
²⁰ Department of Infectious Diseases and Tropical Medicine, London Northwest University Healthcare, London, UK.
²¹ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
²² The Adam Practice, Poole, UK.
²³ NIHR Oxford Biomedical Research Centre, Oxford, UK.
²⁴ NIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, UK.
²⁵ Public Health Wales, Betsi Cadwaladr University Health Board, Bangor University, Bangor, UK.
²⁶ University of Liverpool, Liverpool, UK.
²⁷ University Hospitals of Leicester NHS Trust, University of Leicester, Leicester, UK.
²⁸ Bradford Institute for Health Research and Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
²⁹ Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK.
³⁰ Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.
³¹ Queen Elizabeth University Hospital, NHS Greater Glasgow & Clyde, Glasgow, UK; MRC University of Glasgow Centre for Virus Research, Glasgow, UK.
³² UK Health Security Agency, Porton Down, UK.
³³ UK Health Security Agency, Colindale, London, UK.
³⁴ Division of Epidemiology and Public Health, University of Nottingham School of Medicine.
³⁵ 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: [email protected].

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.

Keywords: COVID-19 vaccine; Fractional dose; Heterologous boost; Homologous boost; Immunogenicity; Persistence; Third dose.

Publication types

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

MeSH terms

Ad26COVS1
Adult
Aged
Aged, 80 and over
Antibodies, Viral
BNT162 Vaccine
COVID-19 Vaccines
COVID-19* / prevention & control
ChAdOx1 nCoV-19
Humans
Immunogenicity, Vaccine
Immunoglobulin G
Middle Aged
SARS-CoV-2
United Kingdom
Viral Vaccines*
mRNA Vaccines

Substances

Ad26COVS1
Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G
Viral Vaccines
mRNA Vaccines
ChAdOx1 nCoV-19
BNT162 Vaccine

Abstract

Publication types

MeSH terms

Substances

Grants and funding