Publication:
Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial

4

Issued Date

2021-08-01

Resource Type

Article

ISSN

23523018

DOI

10.1016/S2352-3018(21)00103-X

Other identifier(s)

2-s2.0-85111351331

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet HIV. Vol.8, No.8 (2021), e474-e485

Suggested Citation

John Frater, Katie J. Ewer, Ane Ogbe, Mathew Pace, Sandra Adele, Emily Adland, Jasmini Alagaratnam, Parvinder K. Aley, Mohammad Ali, M. Azim Ansari, Anna Bara, Mustapha Bittaye, Samantha Broadhead, Anthony Brown, Helen Brown, Federica Cappuccini, Enya Cooney, Wanwisa Dejnirattisai, Christina Dold, Cassandra Fairhead, Henry Fok, Pedro M. Folegatti, Jamie Fowler, Charlotte Gibbs, Anna L. Goodman, Daniel Jenkin, Mathew Jones, Rebecca Makinson, Natalie G. Marchevsky, Yama F. Mujadidi, Hanna Nguyen, Lucia Parolini, Claire Petersen, Emma Plested, Katrina M. Pollock, Maheshi N. Ramasamy, Sarah Rhead, Hannah Robinson, Nicola Robinson, Patpong Rongkard, Fiona Ryan, Sonia Serrano, Timothy Tipoe, Merryn Voysey, Anele Waters, Panagiota Zacharopoulou, Eleanor Barnes, Susanna Dunachie, Philip Goulder, Paul Klenerman, Gavin R. Screaton, Alan Winston, Adrian V.S. Hill, Sarah C. Gilbert, Andrew J. Pollard, Sarah Fidler, Julie Fox, Teresa Lambe, Marion E.E. Watson, Rinn Song, Paola Cicconi, Angela M. Minassian, Sagida Bibi, Simon Kerridge, Nisha Singh, Catherine M. Green, Alexander D. Douglas, Alison M. Lawrie, Elizabeth A. Clutterbuck Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial. The Lancet HIV. Vol.8, No.8 (2021), e474-e485. doi:10.1016/S2352-3018(21)00103-X Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/77248

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Title

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial

Author(s)

John Frater
 Katie J. Ewer
 Ane Ogbe
 Mathew Pace
 Sandra Adele
 Emily Adland
 Jasmini Alagaratnam
 Parvinder K. Aley
 Mohammad Ali
 M. Azim Ansari
 Anna Bara
 Mustapha Bittaye
 Samantha Broadhead
 Anthony Brown
 Helen Brown
 Federica Cappuccini
 Enya Cooney
 Wanwisa Dejnirattisai
 Christina Dold
 Cassandra Fairhead
 Henry Fok
 Pedro M. Folegatti
 Jamie Fowler
 Charlotte Gibbs
 Anna L. Goodman
 Daniel Jenkin
 Mathew Jones
 Rebecca Makinson
 Natalie G. Marchevsky
 Yama F. Mujadidi
 Hanna Nguyen
 Lucia Parolini
 Claire Petersen
 Emma Plested
 Katrina M. Pollock
 Maheshi N. Ramasamy
 Sarah Rhead
 Hannah Robinson
 Nicola Robinson
 Patpong Rongkard
 Fiona Ryan
 Sonia Serrano
 Timothy Tipoe
 Merryn Voysey
 Anele Waters
 Panagiota Zacharopoulou
 Eleanor Barnes
 Susanna Dunachie
 Philip Goulder
 Paul Klenerman
 Gavin R. Screaton
 Alan Winston
 Adrian V.S. Hill
 Sarah C. Gilbert
 Andrew J. Pollard
 Sarah Fidler
 Julie Fox
 Teresa Lambe
 Marion E.E. Watson
 Rinn Song
 Paola Cicconi
 Angela M. Minassian
 Sagida Bibi
 Simon Kerridge
 Nisha Singh
 Catherine M. Green
 Alexander D. Douglas
 Alison M. Lawrie
 Elizabeth A. Clutterbuck

Other Contributor(s)

NIHR Imperial Biomedical Research Centre
 NIHR Oxford Biomedical Research Centre
 NIHR Guy's and St Thomas' Biomedical Research Centre
 Oxford University Hospitals NHS Foundation Trust
 The Wellcome Centre for Human Genetics
 University of Oxford
 St Mary's Hospital
 Imperial College Faculty of Medicine
 Mahidol University
 Nuffield Department of Medicine
 Guy's and St Thomas' NHS Foundation Trust
 University of Oxford Medical Sciences Division

Abstract

Background: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. Methods: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per μL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4–6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing. Findings: Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2–49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per μL (IQR 573·5–859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704–2728]; n=50) and were sustained until day 56 (median 941 EUs [531–1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no 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 people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. 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 Midland's NIHR Clinical Research Network, and AstraZeneca.

Keyword(s)

Immunology and Microbiology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/77248

Collections

Scopus 2021