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

Roshell Muir, Talibah Metcalf, Slim Fourati, Yannic Bartsch, Jacqueline Kyosiimire-Lugemwa, Glenda Canderan, Galit Alter, Enoch Muyanja, Brenda Okech, Teddy Namatovu, Irene Namara, Annemarie Namuniina, Ali Ssetaala, Juliet Mpendo, Annet Nanvubya, Paul Kato Kitandwe, Bernard S. Bagaya, Noah Kiwanuka, Jacent Nassuna, Victoria Menya BiribawaAlison M. Elliott, Claudia J. de Dood, William Senyonga, Priscilla Balungi, Pontiano Kaleebu, Yunia Mayanja, Matthew Odongo, Jennifer Connors, Pat Fast, Matt A. Price, Paul L.A.M. Corstjens, Govert J. van Dam, Anatoli Kamali, Rafick Pierre Sekaly, Elias K. Haddad*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Article numbere0011089
JournalPLoS neglected tropical diseases
Issue number7 July
StatePublished - Jul 2023

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


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