Browsing by Author "Wilson, Shona"

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    Antibody Responses to Schistosoma Mansoni Schistosomula Antigens
    (Parasite immunology, 2018) Egesa, Moses; Lubyayi, Lawrence; Jones, Frances M.; Tukahebwa, Edridah M.; Bagaya, Bernard S.; Dunne, David W.; Elliott, Alison M.; Wilson, Shona; Cose, Stephen
    While antigens from Schistosoma schistosomula have been suggested as potential vaccine candidates, the association between antibody responses with schistosomula antigens and infection intensity at reinfection is not well known. Schistosoma mansoni-infected individuals were recruited from a schistosomiasis endemic area in Uganda (n = 372), treated with 40 mg/kg praziquantel (PZQ) and followed up at five weeks and at one year post-treatment. Pre-treatment and five weeks post-treatment immunoglobulin (Ig) E, IgG1 and IgG4 levels against recombinant schistosomula antigens rSmKK7, rSmLy6A, rSmLy6B and rSmTSP7 were measured using ELISA. Factors associated with detectable pre-treatment or post-treatment antibody response against the schistosomula antigens and the association between five-week antibody responses and one year post-treatment reinfection intensity among antibody responders were examined. Being male was associated with higher pre-treatment IgG1 to rSmKK7, rSmLy6a and AWA. Five weeks post-treatment antibody responses against schistosomula antigens were not associated with one year post-treatment reinfection intensity among antibody responders’ antibody levels against rSmKK7, rSmLy6B and rSmTSP7 dropped, but increased against rSmLy6A, AWA and SEA at five weeks post-treatment among antibody responders. S. mansoni-infected individuals exhibit detectable antibody responses to schistosomula antigens that are affected by treatment. These findings indicate that schistosomula antigens induce highly varied antibody responses and could have implications for vaccine development.
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    Revisiting immunity versus exposure in schistosomiasis: A mathematical modelling study of delayed concomitant immunity
    (Oxford University Press, 2024-10) Milne, Gregory C; Oettle, Rebecca C; Whittaker, Charles; Kabaterine, Narcis B; Basáñez, Maria-Gloria; Webster, Joanne P; Walker, Martin; Wilson, Shona
    Abstract The relative contributions of exposure versus acquired immunity to the epidemiology of human schistosomiasis has been long debated. While there is considerable evidence that humans acquire partial immunity to infection, age- and sex-related contact patterns with water bodies contaminated with infectious cercarial schistosome larvae also contribute to typical epidemiological profiles of infection. Here, we develop a novel schistosome transmission model that incorporates both partially protective ‘delayed concomitant’ acquired immunity—stimulated by dying worms—and host age- and sex-dependent patterns of exposure. We use a contemporary Bayesian approach to fit the model to historical individual data on exposure to infectious cercaria, eggs per gram of faeces (epg), and immunoglobulin E (IgE) antibodies specific to Schistosoma mansoni Tegumental-Allergen-Like protein 1 (SmTAL1) collected from a highly endemic community in Uganda, estimating the relative contributions of exposure and acquired immunity. We find that model variants incorporating or omitting delayed concomitant immunity describe equally well the age- and sex-specific immunoepidemiological patterns observed before intervention and 18 months after treatment. Over longer time-horizons, we find that acquired immunity creates subtle differences in immunoepidemiological profiles during routine mass drug administration that may confer resilience against elimination. We discuss our findings in the broader context of the immunoepidemiology of schistosomiasis.
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    Schistosoma Mansoni schistosomula Antigens Induce Th1/ Pro-inflammatory Cytokine Responses
    (Parasite immunology, 2018) Egesa, Moses; Lubyayi, Lawrence; Tukahebwa, Edridah M.; Bagaya, Bernard S.; Wilson, Shona; Yazdanbakhsh, Maria; Labuda, Lucja A.; Cose, Stephen
    Larvae of Schistosoma (schistosomula) are highly susceptible to host immune responses and are attractive prophylactic vaccine targets, although cellular immune responses against schistosomula antigens in endemic human populations are not well characterized. We collected blood and stool from 54 Schistosoma mansoni-infected Ugandans, isolated peripheral blood mononuclear cells and stimulated them for 24 hours with schistosome adult worm and soluble egg antigens (AWA and SEA), along with schistosomula recombinant proteins rSmKK7, Lymphocyte Antigen 6 isoforms (rSmLy6A and rSmLy6B), tetraspanin isoforms (rSmTSP6 and rSmTSP7). Cytokines, chemokines and growth factors were measured in the culture supernatants using a multiplex luminex assay, and infection intensity was determined before and at 1 year after praziquantel (PZQ) treatment using the Kato-Katz method. Cellular responses were grouped and the relationship between groups of correlated cellular responses and infection intensity before and after PZQ treatment was investigated. AWA and SEA induced mainly Th2 responses. In contrast, rSmLy6B, rSmTSP6 and rSmTSP7 induced Th1/pro-inflammatory responses. While recombinant antigens rSmKK7 and rSmLy6A did not induce a Th1/pro-inflammatory response, they had an association with pre-treatment infection intensity after adjusting for age and sex. Testing more schistosomula antigens using this approach could provide immune-epidemiology identifiers necessary for prioritizing next generation schistosomiasis vaccine candidates.