Protective CMI Mechanism of a Dual-subtype FIV Vaccine

描述：(改编自申请者摘要)主要障碍 HIV疫苗的开发已经确定了一种预防策略， 针对日益增长的艾滋病毒亚型和毒株提供保护，并 确定保护的免疫相关性。为此，我们实验室 已经研究了使用猫的灭活病毒疫苗的方法 免疫缺陷病毒(FIV)-艾滋病的猫模型。针对同源产品的保护 而与之密切相关的FIV毒株已经通过单一毒株疫苗获得， 而对异源亚型的保护甚至明显 相同亚型的异源菌株一直很难。为了 扩大保护性免疫，不同亚型的FIV毒株已被 作为双亚型和三亚型FIV疫苗的免疫原联用。初步 结果表明，在设定的抗原量下，三亚型疫苗是 在保护猫咪方面不如双亚型疫苗有效 相同和不同亚型的异源菌株。此外， 双亚型疫苗在诱导适当的， 检测免疫猫的可重复性免疫反应 病毒中和抗体、细胞毒性T淋巴细胞活性和辅助性T细胞 (Th)活动，包括疫苗诱导的TH-I细胞因子，如 干扰素-伽马。关于哪种类型的免疫力是基本的，存在争议 针对艾滋病病毒的预防性保护和挑战的类型 使用的系统，如静脉注射与粘膜刺激和体内衍生 而不是体外衍生的疫苗。为努力解决这些问题， 来自接种疫苗的猫的无抗体免疫细胞将被过继转移 免疫系统相匹配的猫。免疫系统相匹配的猫 通过骨髓移植发展起来的。在最近的一项初步研究中， 过继转移免疫细胞的接受者被保护不受 同源的FIV挑战。在这项竞争性续签拨款中， 双亚型FIV疫苗诱导的保护性免疫将通过 对免疫系统相匹配的猫进行过继转移研究。我们的 目的是确定双亚型疫苗的细胞免疫机制 针对同源和异源亚型挑战的保护并进行测试 这种保护对黏膜/阴道的挑战是否有效。

DESCRIPTION: (Adapted from Applicant's Abstract) Major obstacles in the development of HIV vaccine have been identifying a prophylactic strategy that affords protection against the growing number of HIV subtypes and strains and determining the immune correlates of protection. To this end, our laboratory has investigated the inactivated virus vaccine approach using the feline immunodeficiency virus (FIV)-cat model of AIDS. Protection against homologous and closely related FIV strains has been achieved with single-strain vaccines, whereas protection against heterologous subtypes and even distinctly heterologous strains of the same subtype has been difficult. In order to broaden the protective immunity, FIV strains from different subtypes have been combined as immunogens of dual- and triple-subtype FIV vaccines. Preliminary results suggest that at a set antigenic dose, the triple-subtype vaccine was not as effective as the dual-subtype vaccine in protecting cats against heterologous strains of same and different subtypes. Furthermore, the dual-subtype vaccine was more effective at eliciting the appropriate, reproducible immune responses in the vaccinated cats with the detection of virus neutralizing antibodies, cytotoxic T Iymphocyte activities, and T-helper (TH) activities including vaccine-induced TH-I cytokines such as interferon-gamma. Controversy exists over what types of immunity are essential for prophylactic protection against AIDS viruses and the types of challenge systems to use such as intravenous versus mucosal challenge and in vivo-derived versus in vitro-derived inoculum. In effort to address these issues, antibody-free immunocytes from vaccinated cats will be adoptively transferred to cats with matched-immune system. Cats with matched-immune systems were developed by bone marrow transplantation. In a recent preliminary study, recipients of the adoptive transfer immunocytes were protected against homologous FIV challenge. In this competitive renewal grant, the correlate of protective immunity induced by dual-subtype FIV vaccine will be identified by performing adoptive transfer studies on cats with matched immune systems. Our goal is to determine the cellular immune mechanisms of dual-subtype vaccine protection against homologous and heterologous subtype challenges and to test whether such protection is effective against mucosal/vaginal challenge.