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Examining the Immunological Effects of COVID-19 Vaccination in Patients with Conditions Potentially Leading to Diminished Immune Response Capacity – The OCTAVE Trial

25 Pages Posted: 23 Aug 2021

See all articles by Pamela Kearns

Pamela Kearns

University of Birmingham - NIHR Birmingham Biomedical Research Centre and Institute of Cancer and Genomic Sciences

Stefan Siebert

University of Glasgow

michelle willicombe

Imperial College London; Imperial College London - Imperial College Healthcare NHS Trust

Charlotte Gaskell

University of Birmingham

Amanda Kirkham

University of Birmingham

Sarah Pirrie

University of Birmingham

Sarah Bowden

University of Birmingham

Sophia Magwaro

University of Birmingham

Ana Hughes

University of Birmingham

Zixiang Lim

University of Oxford

Stavros Dimitriadis

University of Oxford

Sam M. Murray

University of Oxford - Peter Medawar Building for Pathogen Research

Thomas Marjot

University of Oxford

Zay Win

University of Oxford

Sophie L. Irwin

University of Oxford

Georgina Meacham

University of Oxford

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Peter Kelleher

Imperial College London

Jack Satsangi

University of Oxford

Paul Miller

NHS Foundation Trust - St. Georges University Hospitals

Daniel Rea

University Hospitals Birmingham NHS Foundation Trust

Gordon Cook

University of Leeds

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research

Neil Basu

University of Glasgow - Institute of Infection, Immunity and Inflammation

Thushan I. de Silva

University of Sheffield - The Florey Institute for Host-Pathogen Interactions

David Thomas

Imperial College London

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Carl S. Goodyear

University of Glasgow

Iain McInnes

University of Glasgow

More...

Abstract

SARS-COV-2 vaccines have been shown to be efficacious primarily in healthy volunteer populations and population level studies. Immune responses following SARS-CoV-2 vaccination are less well characterised in potentially immune vulnerable patient groups, including those with immune-mediated inflammatory and chronic diseases (inflammatory arthritis [IA] incorporating rheumatoid arthritis [RA] and psoriatic arthritis [PsA]; ANCA-Associated Vasculitis [AAV]; inflammatory bowel disease [IBD]); hepatic disease (HepD), end stage kidney disease requiring haemodialysis (HD) without or with immunosuppression (HDIS); solid cancers (SC) and haematological malignancies (HM), and those that have undergone haemopoietic stem cell transplant (HSCT). The OCTAVE trial is a multi-centre, multi-disease, prospective cohort that will comprehensively assess SARS-CoV-2 vaccine responses within and between the abovementioned disease cohorts using common analytical platforms in patients recruited across the United Kingdom (UK). The majority of subjects received either COVID-19 mRNA Vaccine BNT162b2 (Pfizer/BioNTech) or ChAdOx1 Vaccine (AstraZeneca formerly AZD1222) as part of the UK National COVID19 vaccination programme. As of 13 th August 2021; 2,583 patients have been recruited. We report herein the humoral and T cell immune response results from the first 600 participants recruited where serology data are available at baseline, pre-second vaccine dose (boost) and/or 4 weeks post second dose. We also include in the analysis, data obtained from 231 healthy individuals from the PITCH (Protective Immunity from T cells in Healthcare workers) study. Overall, in comparison to PITCH where 100% of tested individuals (n=93) generated anti-Spike antibodies after vaccine doses, 89% of patients within OCTAVE seroconverted 4 weeks after second vaccine dose. By corollary, approximately 11% of patients across all disease cohorts fail to generate antibodies that react to SARS-CoV-2 spike 4 weeks after two vaccines. Failure to generate spike reactive antibodies was found at a higher proportion in some specific patient subgroups, particularly AAV (72.4%), HD-IS (16.7%) and HepD (16.7%). Importantly, all recruited AAV patients had received Rituximab; a targeted B cell depletion therapy. Furthermore, even in those who seroconverted, 40% of patients across disease cohorts generate lower levels of SARS-CoV-2 antibody reactivity compared to healthy subjects after two SARS-CoV-2 vaccines; the functional significance of these findings in providing protection from subsequent SARS-CoV-2 exposure is not currently known. In contrast to the observed serological response, evaluation of the Spike-specific T cell response revealed that across all patient sub-groups (including AAV) a response similar to healthy individuals was generated. Our data argue strongly for further vaccination strategies to optimise humoral immune responses against SARS-CoV-2 in patients with chronic diseases and/or patients on immune suppressive therapies.

Trial Registration: The trial is registered on ISRCTN 12821688.

Funding: This work was supported by the Medical Research Council COVID-19 Immunity – National Core Study (IMM-NCS) [grant number MC-PC-20031]. Staff at the Cancer Research UK Clinical Trials Unit (CRCTU) are supported by a core funding grant from Cancer Research UK (C22436/A25354). PK and EB are supported by the NIHR Birmingham Biomedical Research Centres at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham Biomedical Research Centres. EB and PK are supported by an NIHR Senior Investigator award. PK is funded by WT109965MA. SJD is funded by an NIHR Global Research Professorship (NIHR300791). TdS is funded by a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z). DS is supported by the NIHR Academic Clinical Lecturer programme in Oxford. LT is supported by the Wellcome Trust (grant number 205228/Z/16/Z), the U.S. Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085. and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. The PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, is funded by the UK Department of Health and Social Care with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UKCIC), the Huo Family Foundation and The National Institute for Health Research (UKRIDHSC COVID-19 Rapid Response Rolling Call, Grant Reference Number COV19-RECPLAS).

Declaration of Interest: None to declare.

Ethical Approval: This study was approved by the UK Medicines and Healthcare Products Regulatory Agency on the 5th February 2021 and the London and Chelsea Research Ethics Committee (REC Ref:21/HRA/0489) on 12th February 2021, with subsequent amendments approved on 3rd March 2021, 19th April 2021 and 26th April 2021).

Suggested Citation

Kearns, Pamela and Siebert, Stefan and willicombe, michelle and Gaskell, Charlotte and Kirkham, Amanda and Pirrie, Sarah and Bowden, Sarah and Magwaro, Sophia and Hughes, Ana and Lim, Zixiang and Dimitriadis, Stavros and Murray, Sam M. and Marjot, Thomas and Win, Zay and Irwin, Sophie L. and Meacham, Georgina and Richter, Alex G. and Kelleher, Peter and Satsangi, Jack and Miller, Paul and Rea, Daniel and Cook, Gordon and Turtle, Lance and Klenerman, Paul and Dunachie, Susanna and Basu, Neil and de Silva, Thushan I. and Thomas, David and Barnes, Eleanor and Goodyear, Carl S. and McInnes, Iain, Examining the Immunological Effects of COVID-19 Vaccination in Patients with Conditions Potentially Leading to Diminished Immune Response Capacity – The OCTAVE Trial. Available at SSRN: https://ssrn.com/abstract=3910058 or http://dx.doi.org/10.2139/ssrn.3910058

Pamela Kearns

University of Birmingham - NIHR Birmingham Biomedical Research Centre and Institute of Cancer and Genomic Sciences ( email )

Birmingham
United Kingdom

Stefan Siebert

University of Glasgow

Michelle Willicombe

Imperial College London ( email )

Centre for Inflammatory Disease, Imperial College
Hammersmith Hospital Campus
London, London W12 0NN
United Kingdom
07803038767 (Phone)

Imperial College London - Imperial College Healthcare NHS Trust

Hammersmith Hospital
London, W12 0HS
United Kingdom

Charlotte Gaskell

University of Birmingham

Edgbaston, B15 2TT
United Kingdom

Amanda Kirkham

University of Birmingham

Edgbaston, B15 2TT
United Kingdom

Sarah Pirrie

University of Birmingham

Edgbaston, B15 2TT
United Kingdom

Sarah Bowden

University of Birmingham

Edgbaston, B15 2TT
United Kingdom

Sophia Magwaro

University of Birmingham

Edgbaston, B15 2TT
United Kingdom

Ana Hughes

University of Birmingham

Edgbaston, B15 2TT
United Kingdom

Zixiang Lim

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Stavros Dimitriadis

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Sam M. Murray

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

Thomas Marjot

University of Oxford

Zay Win

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Sophie L. Irwin

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Georgina Meacham

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences ( email )

Edgbaston
Birminham, Birmingham B152TT
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

Birmingham
United Kingdom

Peter Kelleher

Imperial College London ( email )

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Jack Satsangi

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Paul Miller

NHS Foundation Trust - St. Georges University Hospitals

London
United Kingdom

Daniel Rea

University Hospitals Birmingham NHS Foundation Trust

Mindelsohn Way
Edgbaston
Birmingham, B15 2TH
United Kingdom

Gordon Cook

University of Leeds

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

Neil Basu

University of Glasgow - Institute of Infection, Immunity and Inflammation

Adam Smith Business School
Glasgow, Scotland G12 8LE
United Kingdom

Thushan I. De Silva

University of Sheffield - The Florey Institute for Host-Pathogen Interactions ( email )

David Thomas

Imperial College London

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Carl S. Goodyear (Contact Author)

University of Glasgow

Adam Smith Business School
Glasgow, G12 8LE
United Kingdom

Iain McInnes

University of Glasgow ( email )

Adam Smith Business School
Glasgow, Scotland G12 8LE
United Kingdom

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