Development of a Novel WNV Vaccine that Elicits Protective T Cell Immunity

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TITLE: Development of a novel WNV vaccine that elicits protective T ceil immunity ABSTRACT: Vaccines are being designed and tested that elicit CDB- and CD4-mediated ceilular immunity to WNV. During the previous period of MRCE funding we have defined immunodominant WNV epitopes presented to CDB T ceils by mouse Kb/Db molecules or HLA-A2 molecules. Furthermore, we have shown that COB T ceil lines specific for these immunodominant epitopes confer protection against WNV infection. Using the OVA model system, we have also characterized and further engineered DNA vaccines incorporating class I epitopes into SCTs (¿ingle ghain trimers of peptide-132m-class i heavy chain attached by flexible linkers). We and others have shown that SCT based DNA vaccines elicits potent COB T ceil immunity due to their ability to dispiay a preprocessed, preloaded peptide stabiy as the cell surface. In this current grant we will rigorously test the effectiveness of DNA vaccines encoding SCTs with incorporated immunodominant WNV epitopes. B6 mice and HLA-A2 transgenic mice will be vaccinated and tested for protection against WNV infection. Importantly, we wiil also test novel strategies to target class II epitopes of WNV to endocytic compartments to elicit optimal T ceil help. CD4 T ceil help is predicted to promote the COB T ceil memory response of the vaccine and significantly enhance virus protection. Thus the overail hypothesis of this grant is that coexpressing class II MHC restricted CD4 epitopes along with an SCT that presents a COB epitope wiil elicit enhanced protective ceilular immunity against WNV.