Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

• Type of Material: Article
• Authors: Roshell Muir, Drexel University; Talibah Metcalf, Drexel University; Slim Fourati, Emory University; Yannic Bartsch, Ragon Institute of MGH, MIT, and Harvard, Cambridge; Jacqueline Kyosiimire-Lugemwa, MRC/UVRI and LSHTM Uganda Research Unit; Glenda Canderan, University of Virginia; Galit Alter, Ragon Institute of MGH, MIT, and Harvard, Cambridge; Enoch Muyanja, Emory University; Brenda Okech, UVRI-IAVI HIV Vaccine Program, Entebbe; Teddy Namatovu, UVRI-IAVI HIV Vaccine Program, Entebbe; Irene Namara, UVRI-IAVI HIV Vaccine Program, Entebbe; Annemarie Namuniina, UVRI-IAVI HIV Vaccine Program, Entebbe; Ali Ssetaala, UVRI-IAVI HIV Vaccine Program, Entebbe; Juliet Mpendo, UVRI-IAVI HIV Vaccine Program, Entebbe; Annet Nanvubya, UVRI-IAVI HIV Vaccine PrAliogram, Entebbe; Paul Kato Kitandwe, UVRI-IAVI HIV Vaccine Program, Entebbe; Bernard S Bagaya, Makerere University; Noah Kiwanuka, Makerere University; Jacent Nassuna, Makerere University; Victoria Menya Biribawa, UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.; Alison M Elliott, London School of Hygiene and Tropical Medicine; Claudia J de Dood, Leiden University; William Senyonga, MRC/UVRI and LSHTM Uganda Research Unit; Priscilla Balungi, MRC/UVRI and LSHTM Uganda Research Unit; Pontiano Kaleebu, MRC/UVRI and LSHTM Uganda Research Unit; Yunia Mayanja, MRC/UVRI and LSHTM Uganda Research Unit; Matthew Odongo, MRC/UVRI and LSHTM Uganda Research Unit; Jennifer Connors, Drexel University; Pat Fast, Stanford University; Matt A Price, University of California at San Francisco; Paul L. A. M Corstjens, Leiden University; Govert J van Dam, Leiden University; Anatoli Kamali, UVRI-IAVI HIV Vaccine Program, Entebbe; Rafick-Pierre Sekaly, Emory University; Elias K Haddad, Drexel University
• Language: English
• Date: 2023-07-01
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Muir et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pntd.0011089
• Title of Journal or Parent Work: PLoS Neglected Tropical Diseases
• Volume: 17
• Issue: 7
• Start Page: e0011089
• End Page: e0011089
• Grant/Funding Information: This work was supported by National Institutes of Health funding as part of the Human Immune Project Consortium (HIPC) to EKH and RPS #U19 AI128910 (https://www.nih.gov/). The SiVET study was supported by a grant from the United States Agency for International Development (USAID) [USAID reference number AID-OAA-A-16-00032] (https://www.usaid.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No authors received a salary from the funders.
• Keywords: Immunity; Schistosomiasis mansoni; Animals; Schistosoma mansoni; Vaccination; Antigens, Helminth; Cytokines
• Research Categories: Health Sciences, Public Health; Health Sciences, Immunology; Health Sciences, Pathology; Biology, Biostatistics; Biology, Molecular; Health Sciences, Epidemiology

Abstract

Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vac-cines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vacci-nation serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4+ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower fre-quencies of circulating T follicular helper (cTfh) subpopulations pre-and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abro-gated vaccine responses in communities with endemic infections.