HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway
- Africa Health Research Institute, South Africa
- University of KwaZulu-Natal, South Africa
- International AIDS Vaccine Initiative, United States
- Scripps Research Institute, United States
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
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.
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.
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.
Metrics
-
- 899
- views
-
- 193
- downloads
-
- 10
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway
eLife 11:e79924.
https://doi.org/10.7554/eLife.79924
Further reading
-
- Epidemiology and Global Health
- Microbiology and Infectious Disease
Lack of data on the aetiology of livestock diseases constrains effective interventions to improve livelihoods, food security and public health. Livestock abortion is an important disease syndrome affecting productivity and public health. Several pathogens are associated with livestock abortions but across Africa surveillance data rarely include information from abortions, little is known about aetiology and impacts, and data are not available to inform interventions. This paper describes outcomes from a surveillance platform established in Tanzania spanning pastoral, agropastoral and smallholder systems to investigate causes and impacts of livestock abortion. Abortion events were reported by farmers to livestock field officers (LFO) and on to investigation teams. Events were included if the research team or LFO could attend within 72 hr. If so, samples and questionnaire data were collected to investigate (a) determinants of attribution; (b) patterns of events, including species and breed, previous abortion history, and seasonality; (c) determinants of reporting, investigation and attribution; (d) cases involving zoonotic pathogens. Between 2017–2019, 215 events in cattle (n=71), sheep (n=44), and goats (n=100) were investigated. Attribution, achieved for 19.5% of cases, was significantly affected by delays in obtaining samples. Histopathology proved less useful than PCR due to rapid deterioration of samples. Vaginal swabs provided practical and sensitive material for pathogen detection. Livestock abortion surveillance, even at a small scale, can generate valuable information on causes of disease outbreaks, reproductive losses and can identify pathogens not easily captured through other forms of livestock disease surveillance. This study demonstrated the feasibility of establishing a surveillance system, achieved through engagement of community-based field officers, establishment of practical sample collection and application of molecular diagnostic platforms.
-
- Epidemiology and Global Health
- Genetics and Genomics
Alzheimer’s disease (AD) is a complex degenerative disease of the central nervous system, and elucidating its pathogenesis remains challenging. In this study, we used the inverse-variance weighted (IVW) model as the major analysis method to perform hypothesis-free Mendelian randomization (MR) analysis on the data from MRC IEU OpenGWAS (18,097 exposure traits and 16 AD outcome traits), and conducted sensitivity analysis with six models, to assess the robustness of the IVW results, to identify various classes of risk or protective factors for AD, early-onset AD, and late-onset AD. We generated 400,274 data entries in total, among which the major analysis method of the IVW model consists of 73,129 records with 4840 exposure traits, which fall into 10 categories: Disease, Medical laboratory science, Imaging, Anthropometric, Treatment, Molecular trait, Gut microbiota, Past history, Family history, and Lifestyle trait. More importantly, a freely accessed online platform called MRAD (https://gwasmrad.com/mrad/) has been developed using the Shiny package with MR analysis results. Additionally, novel potential AD therapeutic targets (CD33, TBCA, VPS29, GNAI3, PSME1) are identified, among which CD33 was positively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. TBCA and VPS29 were negatively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. GNAI3 and PSME1 were negatively associated with the main outcome traits of AD, as well as with LOAD, but had no significant causal association with EOAD. The findings of our research advance our understanding of the etiology of AD.
