Human B and T cell responses to novel Schistosoma mansoni skin-stage antigens

Abstract

Background Larvae of Schistosoma (schistosomula) are highly susceptible to host immune responses and are attractive prophylactic vaccine targets. Despite this, cellular and humoral immune responses against schistosomula antigens in endemic human populations are not well characterized. In addition, the association between adaptive immune responses to schistosomula antigens and infection intensity at reinfection is not well-known. Methods To investigate cellular immune responses, peripheral blood mononuclear cells from 54 Schistosoma mansoni-infected Ugandans were stimulated for 24 hours with schistosomula recombinant proteins rSmKK7, rSmLy6A, rSmLy6B and rSmTSP7. Cytokines, chemokines and growth factors were measured in the culture supernatants using a multiplex luminex assay. The cells were examined using flow cytometry for T cell phenotypes associated with resistance to reinfection. Pre-treatment and five-week post-treatment antibody levels against recombinant schistosomula antigens were measured in plasma using ELISA. The plasma was collected from Schistosoma mansoni infected individuals (n=372) recruited from a schistosomiasis endemic area in Uganda, treated with praziquantel and followed up at five weeks and at one-year post-treatment. Factors associated with detectable 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. Results The recombinant antigens induced Th1/pro-inflammatory responses but were not associated with pre-treatment infection intensity after adjusting for age and sex. Being male was associated with higher pre-treatment IgG1 to rSmKK7 and rSmLy6a. Five-week 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. Conclusions Testing more schistosomula antigens using the cluster analysis approach could provide immune-epidemiology identifiers necessary to prioritize the next generation schistosomiasis vaccine candidates. Detectable antibody responses to defined schistosomula antigens were observed but are affected by treatment. These findings indicate that schistosomula antigens induce highly varied antibody responses and could have implications for vaccine development. The data presented in this thesis could inform the selection and prioritization of schistosomiasis vaccine antigens.