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
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 (AZD...
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Immunology and Microbiology Medicine 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 |
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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. |
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NIHR Imperial Biomedical Research Centre |
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NIHR Imperial Biomedical Research Centre 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 |
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Article |
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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 |
author_sort |
John Frater |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publishDate |
2022 |
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https://repository.li.mahidol.ac.th/handle/123456789/77248 |
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1763496065652228096 |
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th-mahidol.772482022-08-04T16:16:58Z 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 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 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 Immunology and Microbiology Medicine 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. 2022-08-04T08:48:55Z 2022-08-04T08:48:55Z 2021-08-01 Article The Lancet HIV. Vol.8, No.8 (2021), e474-e485 10.1016/S2352-3018(21)00103-X 23523018 2-s2.0-85111351331 https://repository.li.mahidol.ac.th/handle/123456789/77248 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85111351331&origin=inward |