Abstract

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 center (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 uncontrolled 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.

Funding: This work was supported by a grant from the Wellcome Trust to the Africa Health Research Institute (Wellcome Trust Strategic Core Award [grant number 201433/Z/16/Z]). Additional funding was received from the South African Department of Science and Innovation through the National Research Foundation (South African Research Chairs Initiative, [grant number 64809]), and the Victor Daitz Foundation.

Data availability

All data generated or analyzed during this study are included in the manuscript and Source data 1.

Article and author information

Author details

  1. Robert Krause

    Africa Health Research Institute, Durban, South Africa
    For correspondence
    robert.krause@ahri.org
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1558-0397
  2. Jumari Snyman

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  3. Hwa Shi-Hsia

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  4. Daniel Muema

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  5. Farina Karim

    School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9698-016X
  6. Yashica Ganga

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  7. Abigail Ngoepe

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  8. Yenzekile Zungu

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  9. Inbal Gazy

    KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    No competing interests declared.
  10. Mallory Bernstein

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  11. Khadija Khan

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7565-7400
  12. Matilda Mazibuko

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  13. Ntombifuthi Mthabela

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  14. Dirhona Ramjit

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  15. COMMIT-KZN Team

  16. Oliver Limbo

    International AIDS Vaccine Initiative, New York, United States
    Competing interests
    No competing interests declared.
  17. Joseph Jardine

    International AIDS Vaccine Initiative, New York, United States
    Competing interests
    No competing interests declared.
  18. Devin Sok

    International AIDS Vaccine Initiative, New York, United States
    Competing interests
    No competing interests declared.
  19. Ian A Wilson

    Scripps Research Institute, La Jolla, United States
    Competing interests
    No competing interests declared.
  20. Willem Hanekom

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  21. Alex Sigal

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    Alex Sigal, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8571-2004
  22. Henrik Kløverpris

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
  23. Thumbi Ndung'u

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2962-3992
  24. Alasdair Leslie

    Africa Health Research Institute, Durban, South Africa
    Competing interests
    No competing interests declared.

Funding

Wellcome Trust (201433/Z/16/Z)

  • Alex Sigal

National Research Foundation (64809)

  • Alex Sigal

Victor Daitz Foundation

  • Alex Sigal

Max Planck Institute for Infection Biology (open access funding)

  • Alex Sigal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Ethics

Human subjects: The study protocol was approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (approval BREC/00001275/2020). Written informed consent was obtained for all enrolled participants.

Version history

  1. Received: May 3, 2022
  2. Preprint posted: June 15, 2022 (view preprint)
  3. Accepted: October 23, 2022
  4. Accepted Manuscript published: October 27, 2022 (version 1)
  5. Version of Record published: November 8, 2022 (version 2)

Copyright

© 2022, Krause et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Robert Krause
  2. Jumari Snyman
  3. Hwa Shi-Hsia
  4. Daniel Muema
  5. Farina Karim
  6. Yashica Ganga
  7. Abigail Ngoepe
  8. Yenzekile Zungu
  9. Inbal Gazy
  10. Mallory Bernstein
  11. Khadija Khan
  12. Matilda Mazibuko
  13. Ntombifuthi Mthabela
  14. Dirhona Ramjit
  15. COMMIT-KZN Team
  16. Oliver Limbo
  17. Joseph Jardine
  18. Devin Sok
  19. Ian A Wilson
  20. Willem Hanekom
  21. Alex Sigal
  22. Henrik Kløverpris
  23. Thumbi Ndung'u
  24. Alasdair Leslie
(2022)
HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway
eLife 11:e79924.
https://doi.org/10.7554/eLife.79924

Share this article

https://doi.org/10.7554/eLife.79924

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