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HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway
- 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,
- COMMIT-KZN Team,
- Oliver Limbo,
- Joseph Jardine,
- Devin Sok,
- Ian A Wilson,
- Willem Hanekom,
- Alex Sigal,
- Henrik Kløverpris,
- Thumbi Ndung'u,
- Alasdair Leslie
Africa Health Research Institute, South Africa; University of KwaZulu-Natal, South Africa; International AIDS Vaccine Initiative, United States; Scripps Research Institute, United States
Oct 27, 2022 - https://doi.org/10.7554/eLife.79924
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.
All data generated or analyzed during this study are included in the manuscript and Source data 1.
Author details
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Jumari Snyman
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Hwa Shi-Hsia
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Daniel Muema
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Yashica Ganga
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Abigail Ngoepe
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Yenzekile Zungu
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Inbal Gazy
KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa
Competing interests
No competing interests declared.
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Mallory Bernstein
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Matilda Mazibuko
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Ntombifuthi Mthabela
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Dirhona Ramjit
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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COMMIT-KZN Team
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Oliver Limbo
International AIDS Vaccine Initiative, New York, United States
Competing interests
No competing interests declared.
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Joseph Jardine
International AIDS Vaccine Initiative, New York, United States
Competing interests
No competing interests declared.
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Devin Sok
International AIDS Vaccine Initiative, New York, United States
Competing interests
No competing interests declared.
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Ian A Wilson
Scripps Research Institute, La Jolla, United States
Competing interests
No competing interests declared.
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Willem Hanekom
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Henrik Kløverpris
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
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Alasdair Leslie
Africa Health Research Institute, Durban, South Africa
Competing interests
No competing interests declared.
Funding
Wellcome Trust (201433/Z/16/Z)
National Research Foundation (64809)
Victor Daitz Foundation
Max Planck Institute for Infection Biology (open access funding)
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
Reviewing Editor
- Bavesh D Kana, University of the Witwatersrand, South Africa
Publication history
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.
Source: eLife https://elifesciences.org/articles/79924
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"This ORCID iD identifies the author of this article:"0000-0003-1558-0397