HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway
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HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway. / Krause, Robert; Snyman, Jumari; Shi-Hsia, Hwa; Muema, Daniel; Karim, Farina; Ganga, Yashica; Ngoepe, Abigail; Zungu, Yenzekile; Gazy, Inbal; Bernstein, Mallory; Khan, Khadija; Mazibuko, Matilda; Mthabela, Ntombifuthi; Ramjit, Dirhona; Limbo, Oliver; Jardine, Joseph; Sok, Devin; Wilson, Ian A.; Hanekom, Willem; Sigal, Alex; Kløverpris, Henrik; Ndung'u, Thumbi; Leslie, Alasdair; COMMIT-KZN Team.
In: eLife, Vol. 11, e79924, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway
AU - Krause, Robert
AU - Snyman, Jumari
AU - Shi-Hsia, Hwa
AU - Muema, Daniel
AU - Karim, Farina
AU - Ganga, Yashica
AU - Ngoepe, Abigail
AU - Zungu, Yenzekile
AU - Gazy, Inbal
AU - Bernstein, Mallory
AU - Khan, Khadija
AU - Mazibuko, Matilda
AU - Mthabela, Ntombifuthi
AU - Ramjit, Dirhona
AU - Limbo, Oliver
AU - Jardine, Joseph
AU - Sok, Devin
AU - Wilson, Ian A.
AU - Hanekom, Willem
AU - Sigal, Alex
AU - Kløverpris, Henrik
AU - Ndung'u, Thumbi
AU - Leslie, Alasdair
AU - COMMIT-KZN Team
N1 - Publisher Copyright: © Krause et al.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.7554/eLife.79924
DO - 10.7554/eLife.79924
M3 - Journal article
C2 - 36300787
AN - SCOPUS:85141894010
VL - 11
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e79924
ER -
ID: 327473918