The goal of this proposal is to define and test synthetic peptide vaccines for schistosomiasis based on B and T cell epitopes from two distinct candidate antigens; STP1 and Sm22 were originally selected via protective monoclonal antibodies. STP1, is triose phosphate isomerase and Sm22 is an integral membrane protein. STP1 is expressed as a full-length, enzymatically and immunologically active molecule in bacteria, Sm22 is expressed as a full-length immunoreactive antigen in a mammalian expression system (COS). Initial experiments determine optimum conditions for vaccinating mice with native and recombinant antigen different syngeneic strains and one outbred strain of mice. The vaccine studies will examine injection routes, antigen dose, and several different adjuvants. We will then utilize chemical and proteolytic cleavage to map B and T cell epitopes for each antigen. Once the individual epitopes have been mapped, corresponding synthetic peptides will be produced and tested to demonstrate that they are immunoreactive with antibodies and lymphocytes prepared against intact antigen. We will then determine if the selected synthetic peptides are immunoreactive with antibodies lymphocytes from patients, chronically infected mice or mice vaccinated with irradiated cercariae. The final goal will be to test the immunoprophylactic potential of individual synthetic peptides well as multiple synthetic peptide constructs (MAPS) in mice. The experiments in this proposal should further schistosome vaccine development in general and will also examine the relationship of epitopes recognized by vaccinated or chronically infected mice and epitopes recognized by patients. Additionally, we will be vaccinating with two relatively novel adjuvant systems: 1)macrophage inhibition factor (MIF); and 2) recombinant STP1 in a BCG expression vector.
The specific aims of the proposal are: 1) To optimize the immunoprophylactic potential of native and recombinant STP1 and Sm22 in 3 syngeneic and one outbred strain of mice; 2) To map the B and T cell epitopes of STP1 and Sm22 recognized by immunized mice; 3) To examine the immunoreactivity of synthetic peptides of STP1 and Sm22 in experimental murine schistosomiasis; and human schistosomiasis; and 4) to test the vaccine potential of synthetic peptides an multiple synthetic peptide constructs of STP1 and Sm22 in mice.
|Da'Dara, Akram A; Skelly, Patrick J; Walker, Christine M et al. (2003) A DNA-prime/protein-boost vaccination regimen enhances Th2 immune responses but not protection following Schistosoma mansoni infection. Parasite Immunol 25:429-37
|Da'dara, Akram A; Skelly, Patrick J; Fatakdawala, Mufaddal et al. (2002) Comparative efficacy of the Schistosoma mansoni nucleic acid vaccine, Sm23, following microseeding or gene gun delivery. Parasite Immunol 24:179-87