MULTISUBTYPE FIV VACCINES

开发艾滋病毒疫苗的一个主要困难是识别 对多种艾滋病毒毒株有效的疫苗接种方法 包括来自不同亚型或分支的田间分离物。一批 艾滋病的动物模型，包括猫免疫缺陷病毒(FIV) 猫的感染，已经被用于测试不同的疫苗方法。我们 使用FIV模型来确定艾滋病毒的疫苗战略。我们的发现 来自FIV疫苗的研究表明，体液和细胞免疫 可能需要对病毒进行全面保护，以防止 异源菌株。同样，对人类艾滋病毒感染的评估 表明强烈的抗HIV体液免疫和细胞免疫都是 延缓疾病发作所必需的。此外，我们还展示了 灭活的FIV和感染细胞疫苗可以保护猫免受 用同源和略有异源的菌株挑战感染 而不是针对不同亚型的菌株。基于这些发现，我们 提出一种广谱艾滋病病毒疫苗可以通过以下方式产生 组合来自不同亚型的原型病毒分离株。这样的一个 两者结合应能引起对FIV的大范围保护性免疫。 我们建议通过开发灭活的多亚型来检验这一假设 由三个亚型(A、B、D)的原型毒株组成的FIV疫苗 并测试其在猫身上的保护效果。接种疫苗的猫将被 监测体液(VN抗体)和细胞(CTL)反应 用同源和异源菌株攻击后。血清和 猫的免疫细胞将在体外测试VN和CTL活性， 分别针对同源和异源菌株，从而 确定这种疫苗是否可以产生广泛的保护作用。这个 保护所需的免疫力类型(S)将由 进行过继转移和被动免疫研究。 将使用免疫细胞(浓缩的)进行过继转移研究 CD4+T细胞、CD8+T细胞、B细胞和单核细胞群) 猫。从接种疫苗的猫的免疫血清中提取抗病毒抗体 提纯并注射给幼稚的猫。 在开发有效的FIV疫苗时，有必要 证明接种疫苗不会导致疫苗产生抗药性 变种。因此，将对多亚型疫苗的开发进行评估 疫苗诱导的变种。

A major difficulty in developing a HIV vaccine has been in identifying a vaccine approach that is effective against a broad range of HIV strains including field isolates from different subtypes or clades. A number of animal models for AIDS, including feline immunodeficiency virus (FIV) infection of cats, have been used to test different vaccine approaches. We have used FIV model to identify vaccine strategies for HIV. Our findings from FIV vaccine studies suggest that both humoral and cellular immunities against the virus may be required to get full protection against heterologous strains. Similarly, evaluation of HIV infection in humans suggest that both strong anti-HIV humoral and cellular immunities are necessary to delay the onset of disease. Further, we have demonstrated that inactivated FIV and infected-cell vaccines can protect cats against challenge infection with homologous and slightly heterologous strains but not against strains from different subtypes. Based on these findings, we propose that a broad-spectrum vaccine for AIDS viruses can be generated by combining prototype virus isolates from different subtypes. Such a combination should elicit a broad-range of protective immunity against FIV. We propose to test this hypothesis by developing inactivated multi-subtype FIV vaccine consisting of prototype strains from three subtypes (A, B, D) and test its protective efficacy in cats. Vaccinated cats will be monitored for humoral (VN antibodies) and cellular (CTL) responses before and after challenge with homologous and heterologous strains. Sera and immunocytes from cats will be tested in vitro for VN and CTL activities, respectively against homologous and heterologous strains, thereby determining if such vaccines can elicit broad-range protection. The type(s) of immunity required for protection will be determined by performing both adoptive transfer and passive immunization studies. Adoptive transfer studies will be performed using immune cells (enriched CD4+ T cell, CD8+ T cell, B cell, and monocyte populations) from vaccinated cats. Antiviral antibodies from Immune serum of vaccinated cats will be purified and administered to naive cats. In the development of an efficacious FIV vaccine, it will be necessary to demonstrate that the vaccination does not induce vaccine resistant variants. Thus, multi-subtype vaccine will be evaluated for development of vaccine-induced variants.