Protective CMI mechanisms of a dual-subtype FIV vaccine

双亚型 FIV 疫苗的保护性 CMI 机制

• 批准号: 7575838
• 负责人: Janet K. Yamamoto
• 金额: $ 9.87万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7575838
• 关键词: AIDS Vaccines; Address; Adoptive Cell Transfers; Adoptive Transfer; Affect; Animals; Antigens; B-Lymphocytes; Binding; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell physiology; Cells; Cellular Immunity; Cytotoxic T-Lymphocytes; Development; Epitopes; Feline Immunodeficiency Virus; Felis catus; Funding; Goals; Grant; HIV; HIV-1; Health; Heterogeneity; Human; Immune; Immune response; Immunity; Immunization; Immunoglobulins; Intravenous; Laboratories; Major Histocompatibility Complex; Mediating; Methods; Natural Killer Cells; Peptides; Phenotype; Population; Prophylactic treatment; Recombinants; Research; Research Design; Resistance; Route; Subfamily lentivirinae; T-Lymphocyte; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Vagina; Variant; Veterinary Medicine; Viral; Viral Proteins; Virus; abstracting; improved; insight; neutralizing antibody; passive antibodies; prophylactic; prototype; response; subcutaneous; transmission process

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.

项目摘要 /摘要 原型和商业双型FIV疫苗，由灭活的亚型和-D组成 菌株，对同源亚型，亚型A/B重组和重组的菌株进行灭菌保护和 异源亚型B挑战。猫在猫中的双重型FIV疫苗保护的机制 应该为人类中有效的HIV-1/艾滋病疫苗的开发提供见解。被动的 用纯化的双重含量FIV疫苗诱导的免疫球蛋白对NA¿VE猫的抗体免疫抑制作用 为受体猫提供保护，免受同源亚型的影响，这与 疫苗诱导的病毒中和抗体的存在（VNA）。相反，被动保护是 通过抗VNA抗性菌株，无法针对异源亚型-B挑战实现。而且，自适应 T细胞富集的人群从接种猫到MHC匹配的猫的转移（A-T）保护了 A-T接受者针对同源和异源挑战。双重型疫苗接种 合并的免疫抑制路线（皮下，皮内，经皮和鼻内） 防止同源阴道挑战。这些结果来自上一个资金周期 建议防止疫苗诱导的VNA启发性菌株（相当亚型） 菌株）由VNA免疫学和细胞介导的免疫学（CMI）介导，而真空保护 抗异源亚型菌株由CMI介导。竞争更新的研究 授予旨在识别T细胞的表型和功能以及病毒表位 以及负责双重型疫苗保护的MHC概况（特定目标1）。提议 研究还将确定最佳的疫苗路线和疫苗保护的机制 反对同源或异源的异源菌株的粘膜阴道挑战 亚型（特定目标2）。这些研究的最终目标是提供有关哪种病毒的见解 组件，宿主免疫反应，MHC轮廓和疫苗路线对 有效预防HIV-1的主要传播模式（粘膜和静脉内） 在人类中。