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. 2025 Mar 26;10(1):56.
doi: 10.1038/s41541-025-01116-x.

Helminth driven gut inflammation and microbial translocation associate with altered vaccine responses in rural Uganda

Jacent Nassuuna #  1 , Joas Sterk #  2 , Bridgious Walusimbi  1   3 , Agnes Natukunda  1   4 , Ronald Nkangi  1   5 , Rebecca Amongin  1 , Ludoviko Zirimenya  1   6 , Emily L Webb  1   4 , Alison M Elliott  1   6 , Gyaviira Nkurunungi  7   8
Affiliations

Helminth driven gut inflammation and microbial translocation associate with altered vaccine responses in rural Uganda

Jacent Nassuuna et al. NPJ Vaccines. .

Abstract

Vaccine responses are sometimes impaired in rural, low-income settings. Helminth-associated gut barrier dysfunction and microbial translocation (MT) may be implicated. We used samples from a trial of praziquantel treatment-effects on vaccine responses in Schistosoma mansoni (Sm)-endemic Ugandan islands, measuring intestinal fatty acid-binding protein 2 (I-FABP2), lipopolysaccharide-binding protein, anti-endotoxin core antibodies (EndoCab), soluble CD14 (sCD14) in plasma, and faecal lipocalin-2, occult blood (FOB), and calprotectin (fCAL), and evaluating their associations with baseline helminth infection, praziquantel treatment, and responses to BCG, yellow fever, typhoid, HPV, and tetanus-diphtheria vaccines. Sm associated positively with fCAL and FOB, hookworm with I-FABP2, and any helminth with EndoCab IgM, fCAL and FOB. Sm associated inversely with sCD14. Praziquantel treatment reduced all marker concentrations, significantly fCAL and FOB, implying that Sm-associated gut inflammation and MT is reversible. Associations of assessed markers with vaccine-specific responses were predominantly inverse. Interventions to improve gut barrier function may enhance vaccine responsiveness.

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Conflict of interest statement

Competing interests: 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, the Royal Society, and DELTAS Africa, outside the submitted work. A.M.E. 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. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study setting.
Fig. 2
Fig. 2. Study schedule.
Samples were collected before vaccinations and/or anthelminthic treatment at relevant timepoints. Only stool and blood samples used for assessment of helminth infections and markers of gut inflammation and microbial translocation are shown. Praziquantel and albendazole were administered to all participants, following the protocol, independent of helminth infection status. Helminth infection status was determined retrospectively, after samples at relevant timepoints had been collected. BCG Bacille Calmette-Guérin, YF-17D Yellow Fever, Ty21a oral typhoid, HPV Human Papillomavirus, Td Tetanus-diphtheria, PZQ praziquantel, CAA circulating anodic antigen, I-FABP2 intestinal fatty acid-binding protein, LBP lipopolysaccharide (LPS)-binding protein, sCD14 soluble CD14, EndoCab anti-endotoxin core antibody, fCAL faecal calprotectin, FOB faecal occult blood, fLcn-2 faecal lipocalin 2. 1Primary endpoint following BCG, YF-17D, Ty21a, and HPV vaccination. 2Primary endpoint following Td vaccination; secondary endpoint following BCG, YF-17D, Ty21a, and HPV vaccination. Created in BioRender. Nkurunungi, G. (2025) https://BioRender.com/y64k537.
Fig. 3
Fig. 3. Effect of baseline helminth infections on levels of markers of gut microbial translocation and gut inflammation.
Forest plot shows adjusted geometric mean ratios (aGMRs) and 95% confidence intervals (CIs) for associations between helminth infections and levels of markers of gut microbial translocation and gut inflammation. Analyses were adjusted for age and sex, and for S. mansoni, trial intervention arm (intensive vs standard praziquantel treatment). Reference category is the uninfected group. The asterisk refers to Infection with any of S. mansoni, hookworm or S. stercoralis. I-FABP2 intestinal fatty acid-binding protein, LBP lipopolysaccharide (LPS) binding protein, sCD14 soluble CD14, EndoCab anti-endotoxin core antibody, fCAL faecal calprotectin, FOB faecal occult blood, fLcn-2 faecal lipocalin 2.
Fig. 4
Fig. 4. Impact of intensive praziquantel treatment on levels of markers of gut microbial translocation and gut inflammation.
Forest plots show geometric mean ratios (GMRs) and 95% confidence intervals (CIs) for associations between praziquantel treatment and levels of markers of gut microbial translocation and gut inflammation, among (a) participants who were S. mansoni infected (CAA ≥ 30 pg/ml) at enrolment (week -6) in both standard and intensive intervention arms, but were S. mansoni negative (CAA < 30 pg/ml) in the intensive arm six weeks later (week 0), and (b) all randomised participants regardless of S. mansoni infection status at enrolment. The reference category for the linear regression model was the standard intervention arm. Sm Schistosoma mansoni, CAA circulating anodic antigen, I-FABP2 intestinal fatty acid-binding protein, LBP lipopolysaccharide (LPS)-binding protein, sCD14 soluble CD14, EndoCab anti-endotoxin core antibodies, fCAL faecal calprotectin, FOB faecal occult blood, fLcn-2 faecal lipocalin-2.
Fig. 5
Fig. 5. Associations between levels of markers of gut microbial translocation/gut inflammation and vaccine responses.
Analyses are adjusted for age and sex. Asterisks represent significant associations. One asterisk represents associations at p < 0.05; two asterisks represent associations at p < 0.01; three asterisks represent associations at p < 0.001. β regression coefficient, I-FABP2 intestinal fatty acid-binding protein, LBP lipopolysaccharide (LPS)-binding protein, sCD14 soluble CD14, EndoCab anti-endotoxin core antibodies, fCAL faecal calprotectin, FOB faecal occult blood, fLcn-2 faecal lipocalin-2.
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