Correlates of protection against SIV/SHIV challenge

抵御 SIV/SHIV 挑战的相关性

• 批准号: 7924012
• 负责人: Hildegund C. J. Ertl
• 金额: $ 274.92万
• 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 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7924012
• 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

本项目的主要目的是使用临床前动物模型阐明免疫介导的抗HIV-1感染保护的相关性。为此，项目1将确定对减毒SIV（称为SIVGY）的体液和细胞介导的免疫反应，该免疫反应可诱导对后续异源致病性SIV攻击的保护性免疫。项目3将使用DNA疫苗、E1缺失腺病毒（Ad）载体和痘病毒载体的组合，确定不同初免-加强疫苗方案引起的免疫应答。项目2将使用中和抗体的被动免疫来确定抗体介导的保护的基线参数，以长期开发诱导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传播中的作用。本计划的第二个目的是确定疫苗诱导的免疫应答（包括Ad载体诱导的免疫应答）是否有害，以及E1缺失的Ad载体的进一步修饰是否可以改善其安全性和免疫原性/有效性。为此，项目3将检验以下假设：针对转基因产物或载体组分的病毒载体疫苗诱导的CD 4 + T细胞应答促进非人灵长类动物SIV感染后的疾病进展。项目1将尝试通过生成和测试第二代E1缺失的Ad载体来改善Ad载体疫苗的有效性和安全性，第二代E1缺失的Ad载体将具有额外的E2 a缺失，以减少Ad载体的高免疫原性结构抗原的合成。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）：疫苗诱导的保护相关性项目2（R。Ruprecht）：CTL疫苗项目3的中和抗体覆盖率（G。Silvestri）：粘液T细胞反应和保护猿猴艾滋病核心A（H。Ertl）：管理核心核心B（X. Zhou）：Vector Core

项目成果

Correlates of relative resistance against low-dose rectal simian immunodeficiency virus challenges in peripheral blood mononuclear cells of vaccinated rhesus macaques.

接种疫苗的恒河猴外周血单核细胞对低剂量直肠猿猴免疫缺陷病毒攻击的相对抵抗力的相关性。

• DOI: 10.1189/jlb.0612287
• 发表时间: 2013
• 期刊: Journal of leukocyte biology
• 影响因子: 5.5
• 作者: Kurupati,Raj;Tuyishime,Steve;Kossenkov,AndrewV;Sazanovich,Marina;Haut,LarissaH;Lasaro,MarcioO;Ratcliffe,SarahJ;Bosinger,StevenE;Carnathan,DianeG;Lewis,Mark;Showe,LouiseC;Silvestri,Guido;Ertl,HildegundCJ
• 通讯作者: Ertl,HildegundCJ