HIV skews the SARS-CoV-2 B cell response towards 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

doi:10.7554/eLife.79924

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

Elife. 2022 Oct 27:11:e79924. doi: 10.7554/eLife.79924.

Authors

Robert Krause^{1

2}, Jumari Snyman^{1

2

3}, Hwa Shi-Hsia^{1

4}, Daniel Muema^{1

2

3}, Farina Karim^{1

2}, Yashica Ganga¹, Abigail Ngoepe¹, Yenzekile Zungu^{1

2}, Inbal Gazy^{2

5}, Mallory Bernstein¹, Khadija Khan^{1

2}, Matilda Mazibuko¹, Ntombifuthi Mthabela¹, Dirhona Ramjit¹; COMMIT-KZN Team; Oliver Limbo²⁰, Joseph Jardine²⁰, Devin Sok²⁰, Ian A Wilson²¹, Willem Hanekom^{1

4}, Alex Sigal^{1

2

22

15}, Henrik Kløverpris^{1

4

23}, Thumbi Ndung'u^{1

2

3

4

22}, Alasdair Leslie^{1

4}

Collaborators

COMMIT-KZN Team:
Moherndran Archary⁶, Kaylesh J Dullabh⁷, Jennifer Giandhari⁵, Philip Goulder⁸, Guy Harling⁹, Rohen Harrichandparsad¹⁰, Kobus Herbst¹¹, Prakash Jeena⁶, Thandeka Khoza¹, Nigel Klein¹², Rajhmun Madansein⁷, Mohlopheni Marakalala¹³, Mosa Moshabela¹⁴, Kogie Naidoo¹⁵, Zaza Ndhlovu¹⁶, Kennedy Nyamande¹⁷, Nesri Padayatchi¹⁵, Vinod Patel¹⁸, Theresa Smit¹, Adrie Steyn¹⁹

Affiliations

¹ Africa Health Research Institute, Durban, South Africa.
² School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
³ HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa.
⁴ Division of Infection and Immunity, University College London, London, United Kingdom.
⁵ KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa.
⁶ Department of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa.
⁷ Department of Cardiothoracic Surgery, University of KwaZulu-Nata, Durban, South Africa.
⁸ Africa Health Research Institute and Department of Paediatrics, Durban, South Africa.
⁹ Africa Health Research Institute and the Institute for Global Health, University College London, London, United Kingdom.
¹⁰ Department of Neurosurgery, University of KwaZulu-Natal, Durban, South Africa.
¹¹ Africa Health Research Institute and the South African Population Research Infrastructure Network, Durban, South Africa.
¹² Africa Health Research Institute and the Institute of Child Health, University College London, London, United Kingdom.
¹³ Africa Health Research Institute and Division of Infection and Immunity, University College London, London, United Kingdom.
¹⁴ College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁵ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
¹⁶ Africa Health Research Institute and the Ragon Institute of MGH, MIT and Harvard, Durban, South Africa.
¹⁷ Department of Pulmonology and Critical Care, University of KwaZulu-Natal, Durban, South Africa.
¹⁸ Vinod Patel, Department of Neurology, University of KwaZulu-Natal, Durban, South Africa.
¹⁹ Africa Health Research Institute and Division of Infectious Diseases, University of Alabama, Birmingham, United States.
²⁰ International AIDS Vaccine Initiative, New York, United States.
²¹ The Scripps Research Institute, La Jolla, United States.
²² Max Planck Institute for Infection Biology, Berlin, Germany.
²³ Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

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 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 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.

Keywords: B cell; COVID-19; HIV; RBD; SARS-CoV-2; epidemiology; global health; human; immunology; inflammation; spike.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
COVID-19*
HIV Infections*
Humans
SARS-CoV-2
South Africa
Spike Glycoprotein, Coronavirus / metabolism

Substances

Spike Glycoprotein, Coronavirus
Antibodies, Viral
spike protein, SARS-CoV-2

Grants and funding

201433/Z/16/Z/WT_/Wellcome Trust/United Kingdom