HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway

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  • Robert Krause
  • Jumari Snyman
  • Hwa Shi-Hsia
  • Daniel Muema
  • Farina Karim
  • Yashica Ganga
  • Abigail Ngoepe
  • Yenzekile Zungu
  • Inbal Gazy
  • Mallory Bernstein
  • Khadija Khan
  • Matilda Mazibuko
  • Ntombifuthi Mthabela
  • Dirhona Ramjit
  • Oliver Limbo
  • Joseph Jardine
  • Devin Sok
  • Ian A. Wilson
  • Willem Hanekom
  • Alex Sigal
  • Kløverpris, Henrik Nyhus
  • Thumbi Ndung'u
  • Alasdair Leslie
  • COMMIT-KZN Team

Background: HIV infection dysregulates the B cell compartment, affecting memory B cell formation and the antibody response to infection and vaccination. Understanding the B cell response to SARS-CoV-2 in people living with HIV (PLWH) may explain the increased morbidity, reduced vaccine efficacy, reduced clearance, and intra-host evolution of SARS-CoV-2 observed in some HIV-1 coinfections. Methods: We compared B cell responses to COVID-19 in PLWH and HIV negative (HIV-ve) patients in a cohort recruited in Durban, South Africa, during the first pandemic wave in July 2020 using detailed flow cytometry phenotyping of longitudinal samples with markers of B cell maturation, homing, and regulatory features. Results: This revealed a coordinated B cell response to COVID-19 that differed significantly between HIV-ve and PLWH. Memory B cells in PLWH displayed evidence of reduced germinal centre (GC) activity, homing capacity, and class-switching responses, with increased PD-L1 expression, and decreased Tfh frequency. This was mirrored by increased extrafollicular (EF) activity, with dynamic changes in activated double negative (DN2) and activated naïve B cells, which correlated with anti-RBD-titres in these individuals. An elevated SARS-CoV-2-specific EF response in PLWH was confirmed using viral spike and RBD bait proteins. Conclusions: Despite similar disease severity, these trends were highest in participants with uncon-trolled HIV, implicating HIV in driving these changes. EF B cell responses are rapid but give rise to lower affinity antibodies, less durable long-term memory, and reduced capacity to adapt to new variants. Further work is needed to determine the long-term effects of HIV on SARS-CoV-2 immunity, particularly as new variants emerge.

Original languageEnglish
Article numbere79924
JournaleLife
Volume11
ISSN2050-084X
DOIs
Publication statusPublished - 2022

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© Krause et al.

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