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

doi:10.1016/j.isci.2022.105862

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

iScience. 2023 Jan 20;26(1):105862. doi: 10.1016/j.isci.2022.105862. Epub 2022 Dec 24.

Authors

Emma Touizer¹, Aljawharah Alrubayyi^{1

2}, Rosemarie Ford¹, Noshin Hussain¹, Pehuén Pereyra Gerber³, Hiu-Long Shum¹, Chloe Rees-Spear¹, Luke Muir¹, Ester Gea-Mallorquí², Jakub Kopycinski², Dylan Jankovic¹, Anna Jeffery-Smith¹, Christopher L Pinder¹, Thomas A Fox¹, Ian Williams⁴, Claire Mullender⁵, Irfaan Maan^{4

5}, Laura Waters⁴, Margaret Johnson^{1

6}, Sara Madge⁶, Michael Youle^{1

6}, Tristan J Barber^{5

6}, Fiona Burns^{5

6}, Sabine Kinloch^{1

6}, Sarah Rowland-Jones², Richard Gilson^{4

5}, Nicholas J Matheson^{3

7}, Emma Morris¹, Dimitra Peppa^{1

4

6}, Laura E McCoy¹

Affiliations

¹ Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK.
² Nuffield Department of Medicine, University of Oxford, Oxford, UK.
³ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge, UK.
⁴ Mortimer Market Centre, Department of HIV, Central and North West London NHS Trust, London, UK.
⁵ Institute for Global Health, University College London, London, UK.
⁶ The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust, London, UK.
⁷ NHS Blood and Transplant, Cambridge, UK.

Abstract

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.

Keywords: Immunology; Virology.

Abstract

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