iScience (Jan 2023)
Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles
- Emma Touizer,
- Aljawharah Alrubayyi,
- Rosemarie Ford,
- Noshin Hussain,
- Pehuén Pereyra Gerber,
- Hiu-Long Shum,
- Chloe Rees-Spear,
- Luke Muir,
- Ester Gea-Mallorquí,
- Jakub Kopycinski,
- Dylan Jankovic,
- Anna Jeffery-Smith,
- Christopher L. Pinder,
- Thomas A. Fox,
- Ian Williams,
- Claire Mullender,
- Irfaan Maan,
- Laura Waters,
- Margaret Johnson,
- Sara Madge,
- Michael Youle,
- Tristan J. Barber,
- Fiona Burns,
- Sabine Kinloch,
- Sarah Rowland-Jones,
- Richard Gilson,
- Nicholas J. Matheson,
- Emma Morris,
- Dimitra Peppa,
- Laura E. McCoy
Affiliations
- Emma Touizer
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Aljawharah Alrubayyi
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Rosemarie Ford
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Noshin Hussain
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Pehuén Pereyra Gerber
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge, UK
- Hiu-Long Shum
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Chloe Rees-Spear
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Luke Muir
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Ester Gea-Mallorquí
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Jakub Kopycinski
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Dylan Jankovic
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Anna Jeffery-Smith
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Christopher L. Pinder
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Thomas A. Fox
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Ian Williams
- Mortimer Market Centre, Department of HIV, Central and North West London NHS Trust, London, UK
- Claire Mullender
- Institute for Global Health, University College London, London, UK
- Irfaan Maan
- Mortimer Market Centre, Department of HIV, Central and North West London NHS Trust, London, UK; Institute for Global Health, University College London, London, UK
- Laura Waters
- Mortimer Market Centre, Department of HIV, Central and North West London NHS Trust, London, UK
- Margaret Johnson
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK; The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK
- Sara Madge
- The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK
- Michael Youle
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK; The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK
- Tristan J. Barber
- Institute for Global Health, University College London, London, UK; The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK
- Fiona Burns
- Institute for Global Health, University College London, London, UK; The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK
- Sabine Kinloch
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK; The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK
- Sarah Rowland-Jones
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Richard Gilson
- Mortimer Market Centre, Department of HIV, Central and North West London NHS Trust, London, UK; Institute for Global Health, University College London, London, UK
- Nicholas J. Matheson
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge, UK; NHS Blood and Transplant, Cambridge, UK
- Emma Morris
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK
- Dimitra Peppa
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK; Mortimer Market Centre, Department of HIV, Central and North West London NHS Trust, London, UK; The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK; Corresponding author
- Laura E. McCoy
- Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK; Corresponding author
- Journal volume & issue
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Vol. 26,
no. 1
p. 105862
Abstract
Summary: We assessed a cohort of people living with human immunodeficiency virus (PLWH) (n = 110) and HIV negative controls (n = 64) after 1, 2 or 3 SARS-CoV-2 vaccine doses. At all timepoints, PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs). Improved neutralization breadth was seen against the Omicron variant (BA.1) after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global MBC dysfunction. In contrast, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, individuals with low or absent neutralization had detectable functional T cell responses. These PLWH had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+T cells after two doses of SARS-CoV-2 vaccination.