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. - 20/05/22

Doi : 10.1016/j.jinf.2022.04.018

Xinxue Liu ^⁎,^1,^{^{#
XL, APSM, SF, and LJ contributed equally as first authors, and SNF, MDS and VC contributed equally as last authors.},}^{^{†
SNF and XL are joint corresponding authors.}} , Alasdair P S Munro ^2,^3,^{^{#
XL, APSM, SF, and LJ contributed equally as first authors, and SNF, MDS and VC contributed equally as last authors.}}, Shuo Feng ^1,^{^{#
XL, APSM, SF, and LJ contributed equally as first authors, and SNF, MDS and VC contributed equally as last authors.}}, Leila Janani ^4,^{^{#
XL, APSM, SF, and LJ contributed equally as first authors, and SNF, MDS and VC contributed equally as last authors.}}, Parvinder K Aley ^1,⁵, Gavin Babbage ², David Baxter ⁶, Marcin Bula ⁷, Katrina Cathie ^2,³, Krishna Chatterjee ⁸, Wanwisa Dejnirattisai ⁹, Kate Dodd ⁷, Yvanne Enever ¹⁰, Ehsaan Qureshi ¹¹, Anna L. Goodman ^12,¹³, Christopher A Green ¹¹, Linda Harndahl ¹⁴, John Haughney ¹⁵, Alexander Hicks ¹⁴, Agatha A. van der Klaauw ¹⁶, Jonathan Kwok ¹⁷, Vincenzo Libri ¹⁸, Martin J Llewelyn ¹⁹, Alastair C McGregor ²⁰, Angela M. Minassian ^1,²¹, Patrick Moore ²², Mehmood Mughal ⁶, Yama F Mujadidi ⁵, Kyra Holliday ²³, Orod Osanlou ²⁴, Rostam Osanlou ²⁵, Daniel R Owens ^2,³, Mihaela Pacurar ^2,³, Adrian Palfreeman ²⁶, Daniel Pan ²⁶, Tommy Rampling ¹⁸, Karen Regan ²⁷, Stephen Saich ², Teona Serafimova ¹², Dinesh Saralaya ²⁷, Gavin R Screaton ⁹, Sunil Sharma ¹⁹, Ray Sheridan ²⁸, Ann Sturdy ²⁰, Piyada Supasa ⁹, Emma C Thomson ^15,²⁹, Shirley Todd ²⁸, Chris Twelves ²³, Robert C. Read ^2,³, Sue Charlton ³⁰, Bassam Hallis ³⁰, Mary Ramsay ³¹, Nick Andrews ³¹, Teresa Lambe ¹, Jonathan S Nguyen-Van-Tam ³², Victoria Cornelius ^4,^{^{#
XL, APSM, SF, and LJ contributed equally as first authors, and SNF, MDS and VC contributed equally as last authors.}}, Matthew D Snape ^1,^5,^{^{#
XL, APSM, SF, and LJ contributed equally as first authors, and SNF, MDS and VC contributed equally as last authors.}}, Saul N Faust ^2,^3,^{^{#
XL, APSM, SF, and LJ contributed equally as first authors, and SNF, MDS and VC contributed equally as last authors.},}^⁎,^{^{†
SNF and XL are joint corresponding authors.}}
the COV-BOOST study group^{^‡}
COV-Boost Study Group authorship – appendix
¹ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
² NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
³ Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK
⁴ Imperial Clinical Trials Unit, Imperial College London, London, UK
⁵ NIHR Oxford Biomedical Research Centre, Oxford, UK
⁶ Stockport NHS Foundation Trust, Stockport, UK
⁷ NIHR Liverpool and Broadgreen Clinical Research Facility, Liverpool, UK
⁸ NIHR Cambridge Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
⁹ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
¹⁰ PHARMExcel. Welwyn Garden City, Hertfordshire, UK
¹¹ NIHR/Wellcome Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
¹² Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK
¹³ 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 Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
²² The Adam Practice, Poole, UK
²³ NIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, UK
²⁴ Public Health Wales, Betsi Cadwaladr University Health Board, Bangor University, Bangor, UK
²⁵ University of Liverpool, Liverpool, UK
²⁶ University Hospitals of Leicester NHS Trust, University of Leicester, Leicester, UK
²⁷ Bradford Institute for Health Research and Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
²⁸ Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK
²⁹ MRC University of Glasgow Centre for Virus Research, Glasgow, UK
³⁰ UK Health Security Agency, Porton Down, UK
³¹ UK Health Security Agency, Colindale, London, UK
³² Division of Epidemiology and Public Health, University of Nottingham School of Medicine

^⁎Corresponding author at: University Hospital Southampton NHS Foundation Trust, NIHR Southampton Clinical Research Facility, Southamptom SO16 6YD, United Kingdom.University Hospital Southampton NHS Foundation TrustNIHR Southampton Clinical Research FacilitySouthamptomSO16 6YDUnited Kingdom^⁎⁎Co-corresponding author at: Xinxue Liu, Oxford Vaccine Group, Centre for Vaccinology and Tropical Medicine, Churchill Hospital, OX3 7LA.Oxford Vaccine GroupCentre for Vaccinology and Tropical MedicineChurchill HospitalOX3 7LA

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Highlights

•	The persistence of humoral responses are different between vaccines.
•	After ChAd/ChAd, mRNA vaccines still have the highest humoral response at day 84.
•	After BNT/BNT viral-vector vaccines have comparable or even higher humoral response at D84 compared with homologous BNT boost schedule.
•	Heterologous and homologous schedules have different kinetics of antibody titre decline by day 84 which appears to depend both on vaccine class and order of administration.
•	Half dose BNT induced comparable levels of humoral and cellular responses at day 84 compared with full dose BNT.

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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.

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

Plan

Introduction

Methods

Trial design & oversight, treatments

Laboratory methods

Statistical analysis

Role of the funding source

Results

Discussion

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Vol 84 - N° 6

P. 795-813 - juin 2022 Retour au numéro

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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. - 20/05/22

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