Protective CMI mechanisms of a dual-subtype FIV vaccine

项目总结/摘要 原型和商业化双亚型FIV疫苗，由灭活亚型A和D组成 菌株，赋予针对同源亚型、亚型A/B重组体的灭菌保护，以及 异源B亚型挑战。FIV双亚型疫苗对猫的免疫保护机制 这将为开发有效的人类HIV-1/AIDS疫苗提供见解。被动 用纯化的双亚型FIV疫苗诱导的免疫球蛋白对初治猫进行抗体免疫 提供了保护受体猫对同源亚型，这与 存在疫苗诱导的病毒中和抗体（VNA）。相比之下，被动保护 对于用VNA抗性菌株进行的异源亚型B攻击，未实现。此外，收养 将T细胞富集群体从接种疫苗的猫转移（A-T）到MHC匹配的猫， A-T受体对抗同源和异源攻击。双亚型疫苗接种， 联合免疫途径（皮下、皮内、经皮和鼻内）提供了 对同种阴道攻击的保护。上一个供资周期的这些结果 提示针对疫苗诱导VNA敏感株（同源亚型）的保护 VNA免疫和细胞介导的免疫（CMI）介导的，而疫苗保护 对异源亚型毒株的免疫抑制作用由CMI介导。竞争性更新的研究 这些研究旨在鉴定T细胞的表型和功能以及病毒表位 和负责双亚型疫苗保护的MHC谱（具体目标1）。拟议 研究还将确定最佳接种途径和疫苗保护机制 用来自同源或异源的异源菌株对抗粘膜-阴道攻击 亚型（具体目标2）。这些研究的最终目标是提供关于哪种病毒 成分、宿主免疫应答、MHC谱和疫苗接种途径对免疫应答至关重要。 有效预防HIV-1的主要传播方式（粘膜和静脉） 在人类身上。

PROJECT SUMMARY / ABSTRACT Prototype and commercial dual-subtype FIV vaccines, consisting of inactivated subtype-A and -D strains, conferred sterilizing protection against homologous subtype, subtype-A/B recombinant, and heterologous subtype-B challenges. The mechanisms of dual-subtype FIV vaccine protection in cats should provide insights to the development of effective HIV-1/AIDS vaccine in humans. Passive antibody immunization with purified dual-subtype FIV vaccine-induced immunoglobulin to na¿ve cats afforded protection of the recipient cats against homologous subtype, which correlated with the presence of vaccine-induced virus neutralizing antibodies (VNA). In contrast, passive protection was not achieved against heterologous subtype-B challenge with VNA-resistant strain. Moreover, adoptive transfer (A-T) of T-cell enriched population from vaccinated cats to MHC-matched cats protected the A-T recipient against homologous and heterologous challenges. Dual-subtype vaccination using combined immunization routes (subcutaneous, intradermal, transcutaneous, & intranasal) afforded protection against homologous vaginal challenge. These results from the previous funding cycle suggest that protection against vaccine-induced VNA-susceptible strains (homologous subtype strains) is mediated by both VNA immunity and cell-mediated immunity (CMI), while vaccine protection against heterologous subtype strains is mediated by CMI. The studies in the competitive renewal grant are aimed at identifying the phenotypes and functions of the T cells as well as the viral epitopes and MHC profiles responsible for the dual-subtype vaccine protection (Specific aim 1). The proposed studies will also identify the best vaccination route(s) and the mechanisms of vaccine protection against mucosal-vaginal challenges with heterologous strains from homologous or heterologous subtype (Specific aim 2). The ultimate goal of these studies is to provide insights about which viral components, host immune responses, MHC profiles, and vaccination routes are important for an effective prophylaxis against the predominant transmission modes (mucosal and intravenous) of HIV-1 in humans.