Abstract
Vaccine immunogenicity varies across populations, yet drivers remain unclear. We compared systemic (plasma) and mucosal (coprological) antibody responses to the oral typhoid vaccine Ty21a, quantified by ELISA, among Ugandan adolescents from urban and Schistosoma mansoni-endemic rural settings. Urban participants elicited higher responses. Causal mediation analysis indicated that S. mansoni partly accounted for reduced mucosal, but not systemic, responses in rural participants, highlighting implications for oral vaccine effectiveness in endemic settings.
Acknowledgements
We thank study participants, their parents and communities for participation, and the Koome sub-county local council, Mukono District authorities, Entebbe Hospital, and Entebbe Municipal Council authorities for supporting the POPVAC trial work. We thank Elizabeth Jones, Andrew Pollard, the Oxford Vaccine Centre Biobank and their study participants for kindly providing control sera for the S. Typhi O:LPS-specific antibody assays; Claudia de Dood, Govert van Dam and Paul Corstjens (Leiden University Medical Center) for production of reagents and support in undertaking the CAA assays. The parent POPVAC programme of work was supported primarily by the Medical Research Council (MRC) of the United Kingdom (grant # MR/R02118X/1 and MC_PC_21034). This award was jointly funded by the UK Medical Research Council (MRC) and the UK Foreign Commonwealth and Development Office (FCDO) under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. GN received support from the EDCTP2 programme supported by the European Union (grant # TMA2019PF-2707) and from the Wellcome Trust (grant # 224263/Z/21/Z). A.N., E.L.W. and A.M.E. received support from the UK National Institute of Health and Care Research (NIHR) under its "NIHR Global Health Research Group on Vaccines for vulnerable people in Africa (VAnguard)” [grant # NIHR134531] using UK aid from the UK Government to support global health research. J.N. was also supported by the Makerere University – Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus), funded under the DELTAS Africa Initiative (grant # DEL-15-004). The DELTAS Africa Initiative was an independent funding scheme of the African Academy of Sciences, Alliance for Accelerating Excellence in Science in Africa and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency with funding from the Wellcome Trust and the UK Government. ELW also received funding through the International Statistics and Epidemiology Group (ISEG) from the UK MRC grant # MR/R010161/1. B.W. was supported by GCRF collaborative Grant (R120442) from the Royal Society awarded to AME. The work was conducted at the MRC/UVRI and LSHTM Uganda Research Unit; both ISEG and the MRC/UVRI and LSHTM Uganda Research Unit are jointly funded by the UK MRC part of UK Research and Innovation and the UK Foreign, Commonwealth and Development Office (FCDO) under the MRC/FCDO Concordat agreement and are also part of the EDCTP2 programme supported by the European Union. The views expressed in this publication are those of the authors and not necessarily those of the funders or the UK government. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report, or in the decision to submit this article for publication.
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G.N. and A.M.E. report grants from Wellcome Trust. G.N. reports funding from the EDCTP2 programme supported by the European Union. A.M.E. reports funding from Medical Research Council (MRC) of the United Kingdom for conduct of the parent study; A.M.E. reports funding from NIH, Science for Africa Foundation and DELTAS Africa, outside the submitted work. B.W. and A.M.E. report funding from the Royal Society outside the submitted work. A.M.E., B.W. and A.N. report support from UK National Institute of Health and care Research (NIHR). A.M.E. further reports support from the Serum Institute of India, Uganda National Expanded Programme on Immunisation, and Emergent BioSolutions for conduct of the parent study. The other authors do not have a competing interest.
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Walusimbi, B., Natukunda, A., Amongin, R. et al. Rural-urban differences in oral typhoid vaccine responses in Uganda: contribution of Schistosoma mansoni. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01484-y
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DOI: https://doi.org/10.1038/s41541-026-01484-y
