The proposed studies should provide significant new data on the influence of HLA Class II type on patient immune responses as well as on clinical outcome. We propose to determine in an isotypic manner, patient antibody titers to native and chemically or enzymatically deglycosylated schistosome antigens, as well as purified or recombinant candidate vaccine antigens. We will test the identical antigens with patient lymphocytes, assaying for proliferation and cytokine product. Further, we will determine cytokine message from lymphocyte subpopulations. The initial correlation of patient clinical status with HLA Class II type has already yielded a significant correlation with hepatosplenic disease. Therefore, it is likely that the data generated in the proposed studies will also lead to predictive markers for resistance/susceptibility. Further, the HLA Class II typing and clinical status generated in these studies will be correlated with results on immunoregulation in schistosomiasis generated in Project II. As the potential for defined antigen vaccines for schistosomiasis draws nearer, a well characterized field site and patient population will be invaluable when trials are performed.
The specific aims of this proposal are: 1) To obtain complete HLA Class II type for all patients in our field site using PCR technology and perform a correlative analysis with patient clinical status; 2) To determine patient antibody responses at the isotype level to native and deglycosylated antigens and recombinant candidate vaccine antigens; 3) To determine patient lymphoproliferative and cytokine responses to native and de-glycosylated and recombinant candidate vaccine antigens; 4) To optimize immunogenicity for humans for the experimental vaccines sTPI and Sm23; 5) To correlate patient immunoreactivity to schistosome antigens with clinical status and HLA Class II type.
| Magalhaes-Santos, Isis F; Lemaire, Denise C; Andrade-Filho, Antonio S et al. (2003) Antibodies to Schistosoma mansoni in human cerebrospinal fluid. Am J Trop Med Hyg 68:294-8 |
| Braga, M D; Coelho, I C; Pompeu, M M et al. (1998) [Control of canine visceral leishmaniasis: comparison of results from a rapid elimination program of serum-reactive dogs using an immunoenzyme assay and slower elimination of serum-reactive dogs using filter paper elution indirect immunofluorescence] Rev Soc Bras Med Trop 31:419-24 |
