Immunogenicity of the Irradiated Schistosoma Mansoni Schistosomula Vaccine.

Abstract

This work was initiated to investigate the immunogenicity of the irradiated schistosomula vaccine with respect to its: ability to protect against challenge infection; ability to induce antibody responses in Western blot (WB) assay; and the antibodies' ability to kill the parasites; ultrastructural changes of the vaccine organism's tegument; antibody binding to their surface in immunofluorescence (IFA) and immunoelectron microscopic (IEM) assays and surface antigen recognition with different sera in WB. Irradiated schistosomula, freshly prepared or cultured up to 48 hours, were able to induce significant levels of protection (27% - 67%). However, irradiated cercariae offered greater protection (52% - 72%). Vaccination of mice with irradiated schistosomula, led to higher antibody responses to adult freeze-thaw (AFT) and schistosomula membrane extract (SME) antigens with respect to time and number of recognized antigens. Most of the in vitro killing of cultured irradiated schistosomula (50% - 95%) was encountered with either vaccinated serum or with heat inactivated vaccinated serum plus complement. Chronic immune serum or complement did not cause more than 20% killing. Normal ultrastructural changes of the tegument of irradiated schistosomula were encountered. Heptalaminate areas were seen after 3 hours of culture and increased thereafter. No decrease in antibody binding to the surface of cultured irradiated schistosomula was seen as measured by IFA and IEM assays. Similar uniform fluorescence as well as substrate reaction were detected on the entire surface of 3 hour, 24 hour and 48 hour old schistosomula. Antigenic profiles of the surface extracts of irradiated and non-irradiated schistosomula were identified using different sera. Pooled human serum (infected patients) and chronic immune mouse serum (12 weeks or 6 months) recognized large numbers of antigens with a wide range of molecular weights (10K -200K). In spite of the few new antigens which appeared or other antigens that disappeared gradually, similar antigenic profiles were encountered. Fewer antigens were recognized by vaccinated serum. An antigen of 100K was identified very strongly compared to the other antigens. In the above studies no differences were encountered between irradiated or non-irradiated schistosomula. Radiation did not alter the presentation of the "protective" antigens since vaccination with cultured schistosomula, even for 48 hours, induced significant protection. Future studies should focus on the effectiveness of vaccinated serum in killing as well as in recognizing surface antigens and use of such antigens, after isolation, for vaccination.