Vaccination of mice with irradiated cercariae of Schistosoma mansoni has been shown to elicit high levels of protection against challenge infection, and this protection can be passively transferred to naive mice. We have identified antigens uniquely recognized by sera of vaccinated mice and have cloned cDNAs encoding three such antigens. The goal of this proposal is to assess the immunoprophylactic potential of these vaccine-specific antigens.
AIM 1. Optimization of the expression of recombinant proteins. The cDNA inserts encoding the three vaccine-specific antigens will be subcloned into a variety of expression vectors, including bacterial and yeast plasmids and vaccinia virus.
AIM 2. Isolation of full length genes encoding vaccine-specific antigens. cDNA inserts of existing clones and of clones that express recombinant gene products recognized by the anti-IrV antiserum (raised against vaccine-specific antigens) will be used as probes to isolated full length genes. These genes will be sequenced, and B- and T-cell reactive domains will be identified.
AIM 3. Assessment of the immunoprophylactic potential of recombinant proteins in vivo. Mice will be immunized with recombinant proteins and the extent of the protection obtained will be assessed by determining the percent reduction in worm burden. The variables to be examined are the vehicle, route, dosage, and interval of administration of the gene products.
AIM 4. Analysis of the immune response of immunized mice. The humoral and cellular immune responses of immunized mice will be assessed by determining the specificity, titer, isotype and kinetics of the humoral response and by determining the extent of T cell proliferation and identity of the T cell subset(s) involved.
AIM 5. Assessment of the immunopathologic potential of recombinant proteins in vivo. Recombinant proteins that exhibit immunoprophylactic potential will be assayed for their role in induction or augmentation of granulomatous responses.
AIM 6. Examination of the potential structural and functional roles of schistosome myosin. The developmental expression and localization of the myosin molecule will be determined and the potential significance of its glycosylation will be assessed.
| Marques Jr Jr, E T; Ichikawa, Y; Strand, M et al. (2001) Fucosyltransferases in Schistosoma mansoni development. Glycobiology 11:249-59 |
