Correlates of protection against SIV/SHIV challenge

抵御 SIV/SHIV 挑战的相关性

• 批准号: 7645935
• 负责人: Hildegund C. J. Ertl
• 金额: $ 283.27万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7645935
• 关键词: Correlates; protection; against; SIV; SHIV

_________________________________________________________________________________________ It is the primary objective of this program to elucidate correlates of immune-mediated protection against HIV-1 infection using pre-clinical animal models. To this end, Project 1 will determine humoral and cell-mediated immune responses to an attenuated SIV, termed SIVGY that induces protective immunity to subsequent challenge with a heterologous pathogenic SIV. Project 3 will determine immune responses elicited by different prime-boost vaccine regimens using combinations of DNA vaccines, E1-deleted adenovirus (Ad) vectors and poxvirus vectors. Project 2 will use passive immunization with neutralizing antibodies to determine baseline parameters of antibody-mediated protection with the long-term to develop vaccines that induce B and T cells. Project 3 will assess the role of vaccine-induced mucosal T cells in limiting the spread of SIV. It is the secondary objective of this program to determine if vaccine-induced immune responses including those induced by Ad vectors can be detrimental and if further modifications of E1-deleted Ad vectors can improve both their safety and immunogenicity/efficacy. To this end, Project 3 will test the hypothesis that CD4+ T cell responses induced by viral vector vaccines against the transgene product or components of the vector facilitate disease progression upon SIV infection of nonhuman primates. Project 1 will attempt to improve the efficacy and safety profile of Ad vector vaccines by generating and testing 2nd generation E1-deleted Ad vectors that will have an additional deletion of E2a to reduce synthesis of the highly immunogenic structural antigens of Ad vectors. The application is subdivided into the following 3 Projects and 2 Cores. Project 1 (H. Ertl): Vaccine-Induced Correlates of Protection Project 2 (R. Ruprecht): Neutralizing Antibody Coverage for CTL Vaccines Project 3 (G. Silvestri): Mucosal T Cell Responses and Protection from Simian AIDS Core A (H. Ertl): Administrative Core Core B (X. Zhou): Vector Core

______________________________________________________________________________________________________ 该计划的主要目的是使用前临床动物模型阐明免疫介导的保护HIV-1感染的保护。为此，项目1将确定对衰减的SIV的体液和细胞介导的免疫反应，称为SIV，称为Sivgy，可诱导保护性免疫，以随后的挑战，并具有异源的致病性SIV。项目3将确定使用DNA疫苗，E1删除的腺病毒（AD）载体和POXVIRUS载体的组合，通过不同的促进疫苗方案引起的免疫反应。项目2将使用中和抗体的被动免疫来确定与长期抗体介导的保护的基线参数，以开发诱导B和T细胞的疫苗。项目3将评估疫苗诱导的粘膜T细胞在限制SIV扩散中的作用。该程序的次要目标是确定疫苗诱导的免疫反应（包括AD载体引起的免疫反应）是否有害，并且是否对E1删除的AD载体进行进一步修改可以提高其安全性和免疫原性/功效。为此，项目3将检验以下假设：病毒载体疫苗针对转基因产物或载体的成分诱导的CD4+ T细胞反应促进了非人类灵长类动物SIV感染后疾病进展。项目1将尝试通过生成和测试第二代E1删除的AD矢量来提高AD载体疫苗的功效和安全性，这些AD矢量将具有额外的E2A缺失，以减少对AD载体的高度免疫性结构抗原的合成。该应用程序被细分为以下3个项目和2个核心。项目1（H. ERTL）：疫苗诱导的保护项目2（R。ruprecht）：CTL疫苗的中和抗体覆盖范围项目3（G。Silvestri）：粘膜T细胞反应和免受Simian AIDS CORES CORES CORES A（H. ERTL）的保护和保护，