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

Autor: Krause, R., Snyman, J., Shi-Hsia, H., Muema, D., Karim, F., Ganga, Y., Ngoepe, A., Zungu, Y., Gazy, I., Bernstein, M., Khan, K., Mazibuko, M., Mthabela, N., Ramjit, D., COMMIT-KZN Team, Limbo, O., Jardine, J., Sok, D., Wilson, I., Hanekom, W., Sigal, A., Kløverpris, H., Ndung'u, T., Leslie, A.
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: eLife
Krause, R, Snyman, J, Shi-Hsia, H, Muema, D, Karim, F, Ganga, Y, Ngoepe, A, Zungu, Y, Gazy, I, Bernstein, M, Khan, K, Mazibuko, M, Mthabela, N, Ramjit, D, Limbo, O, Jardine, J, Sok, D, Wilson, I A, Hanekom, W, Sigal, A, Kløverpris, H, Ndung'u, T, Leslie, A & COMMIT-KZN Team 2022, ' HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway ', eLife, vol. 11, e79924 . https://doi.org/10.7554/eLife.79924
Popis: 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.
Databáze: OpenAIRE
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