{"doi":"10.1101/2022.06.14.496062","title":"HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Funding</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>","journal":null,"year":null,"id":598867,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":805339,"name":"Jumari Snyman","orcid":"0000-0003-4647-8934","position":1,"is_corresponding":false},{"id":1534794,"name":"Hwa Shi-Hsia","orcid":null,"position":2,"is_corresponding":false},{"id":251997,"name":"Daniel Muema","orcid":"0000-0001-7995-1682","position":3,"is_corresponding":false},{"id":406977,"name":"Farina Karim","orcid":"0000-0001-9698-016X","position":4,"is_corresponding":false},{"id":614569,"name":"Yashica Ganga","orcid":"0000-0001-8330-2853","position":5,"is_corresponding":false},{"id":406974,"name":"Abigail Ngoepe","orcid":"0000-0002-1563-647X","position":6,"is_corresponding":false},{"id":709767,"name":"Yenzekile Zungu","orcid":"0000-0002-6577-8599","position":7,"is_corresponding":false},{"id":282140,"name":"Inbal Gazy","orcid":"0000-0003-3944-6977","position":8,"is_corresponding":false},{"id":614567,"name":"Mallory Bernstein","orcid":"0000-0001-7498-2391","position":9,"is_corresponding":false},{"id":614565,"name":"Khadija Khan","orcid":"0000-0001-7565-7400","position":10,"is_corresponding":false},{"id":498499,"name":"Matilda Mazibuko","orcid":null,"position":11,"is_corresponding":false},{"id":616539,"name":"Ntombifuthi Mthabela","orcid":null,"position":12,"is_corresponding":false},{"id":572307,"name":"Dirhona Ramjit","orcid":"0000-0003-0177-9370","position":13,"is_corresponding":false},{"id":550935,"name":"Oliver Limbo","orcid":"0000-0003-1686-1414","position":15,"is_corresponding":false},{"id":1534801,"name":"Joseph Jardine","orcid":null,"position":16,"is_corresponding":false},{"id":108978,"name":"Devin Sok","orcid":"0000-0002-9354-1740","position":17,"is_corresponding":false},{"id":719040,"name":"Ian Wilson","orcid":"0000-0001-6893-2873","position":18,"is_corresponding":false},{"id":1534802,"name":"Willem Hanekom","orcid":null,"position":19,"is_corresponding":false},{"id":584140,"name":"Alex Sigal","orcid":"0000-0001-8571-2004","position":20,"is_corresponding":false},{"id":406978,"name":"Henrik N. Kløverpris","orcid":"0000-0002-2165-3313","position":21,"is_corresponding":false},{"id":252002,"name":"Thumbi Ndung’u","orcid":"0000-0003-2962-3992","position":22,"is_corresponding":false},{"id":104353,"name":"Alasdair Leslie","orcid":"0000-0003-2538-6467","position":23,"is_corresponding":false},{"id":3316,"name":"Robert Krause","orcid":"0000-0003-1558-0397","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Funding</jats:title>\n                  <jats:p>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.</jats:p>\n                </jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W4282976018","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Wellcome Trust","grant_id":"201433","title":"Africa Health Research Institute (GBP record)"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/06/15/2022.06.14.496062.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/06/15/2022.06.14.496062.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2022.06.14.496062","host_type":"publisher"},{"url":"https://doi.org/10.1101/2022.06.14.496062","host_type":"repository"},{"url":"https://europepmc.org/article/PPR/PPR506651","host_type":"Europe_PMC"},{"url":"https://europepmc.org/api/fulltextRepo?pprId=PPR506651&type=FILE&fileName=EMS146984-pdf.pdf&mimeType=application/pdf","host_type":"Europe_PMC"},{"url":"https://doi.org/10.7554/elife.79924","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/36300787","host_type":""},{"url":"http://dx.doi.org/10.7554/eLife.79924","host_type":""},{"url":"https://doaj.org/article/9e85d121845c4a7ba7f4e109a7030fe9","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-000C-2B57-3","host_type":""},{"url":"https://hdl.handle.net/21.11116/0000-000C-2B59-1","host_type":""},{"url":"https://curis.ku.dk/ws/files/327473922/elife_79924_v2.pdf","host_type":""},{"url":"https://researchprofiles.ku.dk/da/publications/7f7c43e0-bdfe-46cd-91c1-ac7bc03f8225","host_type":""},{"url":"https://doi.org/10.7554/eLife.79924","host_type":""},{"url":"https://doi.org/https://doi.org/10.7554/eLife.79924","host_type":""}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","COVID-19 Clinical Research Studies","Immune responses and vaccinations","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Memory B cell","Germinal center","Flow cytometry","B cell","Immunology","Antibody","Cell","Human immunodeficiency virus (HIV)","Virology","T cell","Biology","Cohort","Vaccination","Immune system","Medicine","Internal medicine","Genetics","QH301-705.5","SARS-CoV-2","Science","Q","R","HIV","COVID-19","HIV Infections","spike","Antibodies, Viral","RBD","South Africa","Epidemiology and Global Health","Spike Glycoprotein, Coronavirus","Humans","Biology (General)"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":16,"sdg_label":"16. Peace & justice"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T16:20:29.073417Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}