IMMUNOGENICITY OF ORAL SIV & HIV1 VACCINES

描述：这项研究的长期目标是开发一种现场口述 志贺氏菌-HIV-1疫苗载体诱导HIV-1特异性CD4+和CD8+T细胞 细胞反应。志贺氏菌属对人类是完全致命的，对一种较轻的 延伸到猕猴身上。有一种定义明确的啮齿动物和非人类 灵长类动物模型可用于评价卡介苗的安全性、免疫原性和疗效 候选口服减毒志贺氏菌活疫苗。与L. 单核细胞增多性志贺氏菌--逃离内体隔室并复制 上皮细胞、树突状细胞和巨噬细胞的细胞质 与结肠淋巴组织有关。这一点的中心假设是 那么格兰特就是活的口服减毒志贺氏菌SIV和志贺氏菌HIV-1 疫苗载体诱导MHC I、II类限制性粘膜T细胞 细胞反应。为了解决这一假设，研究人员建议 构建稳定的减毒志贺氏菌SIV和志贺氏菌HIV-1载体 高效表达Gag-Nef融合蛋白并鉴定 使用小鼠模型的免疫原性构建。这些构造是 将对小鼠的免疫原性和抗病毒能力进行评估 对恒河猴的疗效。

DESCRIPTION: The longterm goal of this research is to develop a live oral Shigella-HIV-1 vaccine vector that induces HIV-1 specific CD4+ and CD8+ T cell responses. Shigella spp. are fully virulent in humans and to a lesser extend in Rhesus macaques. There is a well defined rodent and non-human primate model available to evaluate safety, immunogenicity and efficacy of candidate live oral attenuated Shigella-vaccines. Analogous to L. monocytogenes, Shigella- escapes the endosomal compartment and replicates with the cytoplasm of epithelial cells, dendritic cells, and macrophages associated with colonic lymphoid tissue. The central hypothesis of this grant then is that a live oral attenuated Shigella-SIV and Shigella-HIV-1 vaccine vector will induce MHC class I and class II restricted mucosal T cell responses. To address this hypothesis, the investigator proposes to construct attenuated Shigella-SIV and Shigella-HIV-1 vectors that stably express a high level of a Gag-Nef fusion protein and identify the immunogenic constructs using the murine model. The constructs that are immunogenic in mice will be evaluated for immunogenicity and anti viral efficacy in Rhesus macaques.