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Safety and Immunogenicity of the ChAdox1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 in HIV Infection

39 Pages Posted: 19 Apr 2021

See all articles by John Frater

John Frater

University of Oxford

Katie Ewer

University of Oxford - Jenner Institute

Ane Ogbe

University of Oxford - Peter Medawar Building for Pathogen Research

Matthew Pace

University of Oxford - Peter Medawar Building for Pathogen Research

Sandra Adele

University of Oxford - Peter Medawar Building for Pathogen Research

Emily Adland

University of Oxford - Peter Medawar Building for Pathogen Research

Jasmini Alagaratnam

Imperial College London - Department of Infectious Disease

Parvinder K. Aley

University of Oxford - Oxford Vaccine Group

Mohammad Ali

University of Oxford - Peter Medawar Building for Pathogen Research

M. Azim Ansari

University of Oxford - Peter Medawar Building for Pathogen Research

Anna Bara

NIHR Imperial Clinical Research Facility

Mustapha Bittaye

University of Oxford - The Jenner Institute

Sam Broadhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Anthony Brown

University of Oxford - Peter Medawar Building for Pathogen Research

Helen Brown

University of Oxford - Peter Medawar Building for Pathogen Research

Federica Cappuccini

University of Oxford - The Jenner Institute

Enya Cooney

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Wanwisa Dejnirattisai

University of Oxford - Wellcome Centre for Human Genetics

Christina Dold

University of Oxford - Oxford Vaccine Group

Cassandra Fairhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Henry Fok

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Pedro M. Folegatti

University of Oxford - Jenner Institute

Jamie Fowler

University of Oxford - The Jenner Institute

Charlotte Gibbs

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Anna L. Goodman

University College London - Department of Infection

Daniel Jenkin

University of Oxford - Jenner Institute

Mathew Jones

University of Oxford - Peter Medawar Building for Pathogen Research

Rebecca Makinson

University of Oxford - The Jenner Institute

Natalie G. Marchevsky

University of Oxford - Oxford Vaccine Group

Yama Farooq Mujadidi

University of Oxford - Oxford Vaccine Group

Hanna Nguyen

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Lucia Parolini

University of Oxford - Peter Medawar Building for Pathogen Research

Claire Petersen

Imperial College London - Department of Infectious Disease

Emma Plested

University of Oxford - Oxford Vaccine Group

Katrina M. Pollock

NIHR Imperial Clinical Research Facility

Maheshi N. Ramasamy

University of Oxford - Oxford Vaccine Group

Sarah Rhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Hannah Robinson

University of Oxford - Oxford Vaccine Group

Nicola Robinson

University of Oxford - Peter Medawar Building for Pathogen Research

Patpong Rongkard

University of Oxford - Peter Medawar Building for Pathogen Research

Fiona Ryan

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Sonia Serrano

NIHR Guy's and St Thomas' Biomedical Research Centre

Helen Stockmann

Imperial College London - Department of Infectious Disease

Timothy Tipoe

University of Oxford - Peter Medawar Building for Pathogen Research

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Anele Waters

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Panagiota Zacharopoulou

University of Oxford - Peter Medawar Building for Pathogen Research

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research

Philip Goulder

University of Oxford - Department of Paediatrics

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research

Gavin Screaton

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

Alan Winston

Imperial College London - Department of Infectious Disease

Adrian V. S. Hill

University of Oxford - Wellcome Trust Centre for Human Genetics; University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Sarah C. Gilbert

University of Oxford - The Jenner Institute

Andrew Pollard

University of Oxford - Oxford Vaccine Group

Sarah Fidler

Imperial College London - Department of Medicine

Julie Fox

Guy's and St Thomas' NHS Foundation Trust - Harrison Wing

Teresa Lambe

University of Oxford - Jenner Institute

Oxford COVID Vaccine Trial Group

More...

Abstract

Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine is immunogenic and protects against COVID-19. However, data on vaccine immunogenicity are needed for the 40 million people living with HIV (PWH), who may have less functional immunity and more associated co-morbidities than the general population.

Methods: Between the 5th and 24th November 2020, 54 adults with HIV, aged 18-55 years, were enrolled into a single arm open label vaccination study within the protocol of the larger phase 2/3 COV002 trial. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses (5 × 1010 vp) was given 4-6 weeks apart. All participants were on antiretroviral therapy (ART) with undetectable plasma HIV viral loads and CD4+ T cell counts >350 cells/µl at enrolment. Data were captured on adverse events. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo interferon-γ enzyme-linked immunospot assay (ELISpot) and T cell proliferation. All outcomes were compared with a HIV uninfected group from the main COV002 study.

Findings: 54 participants with HIV (median age 42.5 years (IQR 37.2-49.8)) received two doses of ChAdOx1 nCoV-19. Median CD4+ T cell count at enrolment was 694 cells/µl (IQR 562-864). Results are reported for 56 days of follow-up. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (49%), fatigue (47%), headache (47%), malaise (34%), chills (23%), and muscle or (36%) joint pain (9%), the frequencies of which were similar to the HIV-negative participants. There were no serious adverse events. Anti-spike IgG responses by ELISA peaked at Day 42 (median 1440 ELISA units, IQR 704-2728) and were sustained out to Day 56. There was no correlation with CD4+ T cell count or age and the magnitude of the anti-spike IgG response at Day 56 (P>0.05 for both). ELISpot and T cell proliferative responses peaked between Day 14 and 28 after prime and were sustained through to Day 56. When compared to participants without HIV there was no statistical difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (P>0.05 for all analyses).

Interpretation: In this study of PWH, vaccination with ChAdOx1 nCoV-19 was well tolerated and there was no difference in humoral and cell-mediated immune responses compared to an adult cohort without HIV who received the same vaccination regime.

Trial Registration: Trial Registration number is NCT04400838.

Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Declaration of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19 (AZD1222). AstraZeneca reviewed the data from the study and the final manuscript before 474 submission, but the authors retained editorial control. SCG is cofounder of Vaccitech (a collaborator in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AVSH is a cofounder of and consultant to Vaccitech and is named as an inventor on a patent covering design and use of ChAdOx1-vectored vaccines (PCT/GB2012/000467).

Ethical Approval: Written informed consent was obtained from all participants, and the trial was done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. This study was approved in the UK by the Medicines and Healthcare products Regulatory Agency (reference 21584/0424/001-0001) and the South Central Berkshire Research Ethics Committee (reference 20/SC/0145). Vaccine use was authorised by Genetically Modified Organisms Safety Committees at each participating site.

Suggested Citation

Frater, John and Ewer, Katie and Ogbe, Ane and Pace, Matthew and Adele, Sandra and Adland, Emily and Alagaratnam, Jasmini and Aley, Parvinder K. and Ali, Mohammad and Ansari, M. Azim and Bara, Anna and Bittaye, Mustapha and Broadhead, Sam and Brown, Anthony and Brown, Helen and Cappuccini, Federica and Cooney, Enya and Dejnirattisai, Wanwisa and Dold, Christina and Fairhead, Cassandra and Fok, Henry and Folegatti, Pedro M. and Fowler, Jamie and Gibbs, Charlotte and Goodman, Anna L. and Jenkin, Daniel and Jones, Mathew and Makinson, Rebecca and Marchevsky, Natalie G. and Farooq Mujadidi, Yama and Nguyen, Hanna and Parolini, Lucia and Petersen, Claire and Plested, Emma and Pollock, Katrina M. and Ramasamy, Maheshi N. and Rhead, Sarah and Robinson, Hannah and Robinson, Nicola and Rongkard, Patpong and Ryan, Fiona and Serrano, Sonia and Stockmann, Helen and Tipoe, Timothy and Voysey, Merryn and Waters, Anele and Zacharopoulou, Panagiota and Barnes, Eleanor and Dunachie, Susanna and Goulder, Philip and Klenerman, Paul and Screaton, Gavin and Winston, Alan and Hill, Adrian V. S. and Gilbert, Sarah C. and Pollard, Andrew and Fidler, Sarah and Fox, Julie and Lambe, Teresa and Group, Oxford COVID Vaccine Trial, Safety and Immunogenicity of the ChAdox1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 in HIV Infection. Available at SSRN: https://ssrn.com/abstract=3829931 or http://dx.doi.org/10.2139/ssrn.3829931

John Frater (Contact Author)

University of Oxford

Katie Ewer

University of Oxford - Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Ane Ogbe

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Matthew Pace

University of Oxford - Peter Medawar Building for Pathogen Research

Sandra Adele

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

South Parks Road
OX2 3SY
United Kingdom

Emily Adland

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Jasmini Alagaratnam

Imperial College London - Department of Infectious Disease ( email )

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

Parvinder K. Aley

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Mohammad Ali

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

M. Azim Ansari

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Anna Bara

NIHR Imperial Clinical Research Facility ( email )

Du Cane Rd
Shepherd's Bush
London, W12 0HS
United Kingdom

Mustapha Bittaye

University of Oxford - The Jenner Institute ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Sam Broadhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Anthony Brown

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Helen Brown

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Federica Cappuccini

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Enya Cooney

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Wanwisa Dejnirattisai

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Christina Dold

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Cassandra Fairhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Henry Fok

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Pedro M. Folegatti

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Jamie Fowler

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Charlotte Gibbs

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Anna L. Goodman

University College London - Department of Infection ( email )

Gower Street
London, WC1E 6BT
United Kingdom

Daniel Jenkin

University of Oxford - Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Mathew Jones

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Rebecca Makinson

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Natalie G. Marchevsky

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Yama Farooq Mujadidi

University of Oxford - Oxford Vaccine Group

Hanna Nguyen

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Lucia Parolini

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Claire Petersen

Imperial College London - Department of Infectious Disease ( email )

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

Emma Plested

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Katrina M. Pollock

NIHR Imperial Clinical Research Facility

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

Maheshi N. Ramasamy

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Sarah Rhead

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Hannah Robinson

University of Oxford - Oxford Vaccine Group

Oxford
United Kingdom

Nicola Robinson

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Patpong Rongkard

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Fiona Ryan

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Sonia Serrano

NIHR Guy's and St Thomas' Biomedical Research Centre

London, SE1 9RT
United Kingdom

Helen Stockmann

Imperial College London - Department of Infectious Disease ( email )

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

Timothy Tipoe

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Anele Waters

Guy's and St Thomas' NHS Foundation Trust - Department of Infection ( email )

London
United Kingdom

Panagiota Zacharopoulou

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Susanna Dunachie

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

South Parks Road
OX2 3SY
United Kingdom

Philip Goulder

University of Oxford - Department of Paediatrics

United Kingdom

Paul Klenerman

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

South Parks Road
OX2 3SY
United Kingdom

Gavin Screaton

Guy's and St Thomas' NHS Foundation Trust - Department of Infection

London
United Kingdom

Alan Winston

Imperial College London - Department of Infectious Disease ( email )

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

Adrian V. S. Hill

University of Oxford - Wellcome Trust Centre for Human Genetics ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Sarah C. Gilbert

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Andrew Pollard

University of Oxford - Oxford Vaccine Group ( email )

United Kingdom

Sarah Fidler

Imperial College London - Department of Medicine ( email )

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

Julie Fox

Guy's and St Thomas' NHS Foundation Trust - Harrison Wing

United Kingdom

Teresa Lambe

University of Oxford - Jenner Institute ( email )

No contact information is available for Oxford COVID Vaccine Trial Group

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