TITLE: Development of a novel WNV vaccine that elicits protective T ceil immunityABSTRACT: Vaccines are being designed and tested that elicit CDB- and CD4-mediated ceilularimmunity to WNV. During the previous period of MRCE funding we have defined immunodominantWNV 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 epitopesconfer protection against WNV infection. Using the OVA model system, we have also characterizedand further engineered DNA vaccines incorporating class I epitopes into SCTs ( ingle ghain trimersof peptide-132m-class i heavy chain attached by flexible linkers). We and others have shown thatSCT based DNA vaccines elicits potent COB T ceil immunity due to their ability to dispiay apreprocessed, preloaded peptide stabiy as the cell surface. In this current grant we will rigorouslytest the effectiveness of DNA vaccines encoding SCTs with incorporated immunodominant WNVepitopes. B6 mice and HLA-A2 transgenic mice will be vaccinated and tested for protection againstWNV infection. Importantly, we wiil also test novel strategies to target class II epitopes of WNV toendocytic compartments to elicit optimal T ceil help. CD4 T ceil help is predicted to promote theCOB T ceil memory response of the vaccine and significantly enhance virus protection. Thus theoverail hypothesis of this grant is that coexpressing class II MHC restricted CD4 epitopes along withan SCT that presents a COB epitope wiil elicit enhanced protective ceilular immunity against WNV.
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