The project seeks to assess the vaccine potential of several non-variant surface antigens found in the economically important trypanosomal subspecies relevant to human disease in Africa. First, the set of genes encoding these antigenes (transmembrane adenylate cyclases ESAG 4 and GRESAG 4, p-type ATPase TBA 1) in each of a series of stocks from the field of the relevant subspecies (T. brucei gambienne, T. brucei rhodesiense) will be surveyed and compared with the same gene set in the particular stock of T. brucei, which we have already cloned and sequenced, in order to identify the similarities and differences between each subspecies and actual variants recently isolated from the field within subspecies. This comparison will greatly facilitate the selection of antigens or antigen fragments with the most highly conserved distribution in order to ensure development of a vaccine with the widest applicability. The survey will use a strategy of gene cloning and sequencing, thus permiting subsequent genetic engineering and expression in eukaryotic cell systems designed to produce large quantities of the engineered extracellular of each antigen.
The engineered antigens will be produced in quantity and used to develop for circulating antibodies in infected animals, for the production of antibody reagents in order to assay circulating antigens and for the assessment of their protective effect in experimental animals against challenge with live parasites.
Sufficient structural studies and modeling of the antigens will be undertaken in order to aid the genetic engineering and the initial vaccine development. Studies designed to optimize the immunization protocol will also be performed. Finally, a limited number of functional studies will be completed in order to explore the possible ways that these antibodies might be interfering with cell function.
Funding SchemeCSC - Cost-sharing contracts