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: 7547369
• 负责人: Janet K. Yamamoto
• 金额: $ 29.6万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7547369
• 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; Dose; Epitopes; Failure; Feline Acquired Immunodeficiency Syndrome; Feline Immunodeficiency Virus; Felis catus; Funding; Goals; Grant; HIV; HIV-1; HIV-1 vaccine; Health; Heterogeneity; Human; Immune; Immune response; Immunity; Immunization; Immunoglobulins; Intravenous; Laboratories; Major Histocompatibility Complex; Mediating; Methods; Natural Killer Cells; Peptides; Phenotype; Population; Prevalence; Prophylactic treatment; Public Health; 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; concept; design; improved; insight; neutralizing antibody; passive antibodies; prophylactic; prototype; response; subcutaneous; transmission process

DESCRIPTION (provided by applicant): 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 naive 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. PUBLIC HEALTH RELEVANCE: Over 1.8 million doses of commercial feline immunodeficiency virus (FIV) vaccine have been sold since July 2002 without any cases of vaccine failure. FIV causes feline AIDS in pet cats and has worldwide prevalence similar to HIV-1. The mechanisms of this FIV vaccine protection and viral proteins important for such protection will be determined in the proposed studies of this grant. Findings from these studies should advance our understanding about how to design an effective HIV-1 vaccine in humans.

描述（由申请人提供）：原型和商业双囊型FIV疫苗，由灭活的亚型A和-D菌株组成，对同源亚型，亚型A/B重组和异态亚型B挑战进行了对同源亚型，亚型A/B子类型的施用保护保护。猫在猫中的双重型FIV疫苗保护的机制应为人类有效的HIV-1/艾滋病疫苗的发展提供见解。用纯化的双囊型FIV疫苗诱导的对天真猫的免疫球蛋白进行的被动抗体免疫可保护受体猫免受同源亚型的影响，这与疫苗诱导的病毒中和中和抗体（VNA）的存在相关。相反，没有通过抗VNA抗性菌株来抵抗异源亚型-B挑战的被动保护。此外，从接种猫到MHC匹配的猫的T-Cell富含人群的收养转移（A-T）保护了A-T受体免受同源和异源挑战。使用联合免疫途径（皮下，皮内，经皮和鼻内）的双重型疫苗接种，可保护免受同源阴道挑战的保护。先前资金周期的这些结果表明，对疫苗诱导的VNA敏感性菌株（同源亚型菌株）的保护是由VNA免疫和细胞介导的免疫（CMI）介导的，而疫苗保护针对异源亚型菌株的保护是由CMI介导的。竞争性更新赠款中的研究旨在识别T细胞的表型和功能，以及负责双重亚型疫苗保护的病毒表位和MHC概况（特定目标1）。拟议的研究还将确定最佳的疫苗接种途径以及疫苗保护的机制，以防止与同源或异源亚型的异源菌株相比，针对粘膜阴道挑战（特定目标2）。这些研究的最终目的是提供有关哪些病毒成分，免疫反应，MHC概况和疫苗接种途径的见解，对于人类中HIV-1的主要传播模式（粘膜和静脉内）的有效预防至关重要。公共卫生相关性：自2002年7月以来，出售了超过180万剂的商业猫免疫缺陷病毒（FIV）疫苗，而没有任何疫苗失败。 FIV会引起宠物猫的猫咪援助，并且在全球范围内类似于HIV-1。该FIV疫苗保护和病毒蛋白对此类保护的重要机制将在该赠款的拟议研究中确定。这些研究的发现应提高我们对如何在人类中设计有效的HIV-1疫苗的理解。