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

标题：开发一种增强保护性T细胞免疫的新型WNV疫苗 摘要：目前正在设计和测试能够诱导CDB和CD 4介导的细胞凋亡的疫苗。 对西尼罗河病毒免疫。在MRCE资助的前一阶段，我们定义了免疫显性 小鼠Kb/Db分子或HLA-A2分子递呈给CDB T细胞的WNV表位。 此外，我们已经表明，对这些免疫显性表位特异的COB T细胞系， 保护免受西尼罗河病毒感染。使用OVA模型系统，我们还表征了 以及进一步将I类表位并入SCT的工程化DNA疫苗（单链三聚体 通过柔性接头连接的肽-132M-I类重链）。我们和其他人已经证明， 基于SCT的DNA疫苗由于其展示免疫原性的能力而增强了有效的COB T细胞免疫。 预处理的、预装载的肽稳定地作为细胞表面。在目前的拨款中，我们将严格 测试编码SCT的DNA疫苗与并入的免疫显性WNV的有效性 表位B6小鼠和HLA-A2转基因小鼠将接种疫苗并测试针对以下的保护： 西尼罗河病毒感染。重要的是，我们还将测试靶向西尼罗河病毒II类表位的新策略， 内吞区室以引发最佳T细胞帮助。预计CD 4 T细胞帮助可以促进 COB T细胞对疫苗的记忆应答和显著增强病毒保护作用。因此 这项授权的总体假设是，共表达II类MHC限制性CD 4表位沿着 呈递COB表位的SCT将引发针对WNV的增强的保护性细胞免疫。

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.