Protective CMI Mechanism of a Dual-subtype FIV Vaccine

描述：（改编自申请人的摘要） HIV疫苗的开发已经确定了一种预防策略， 提供保护，防止越来越多的艾滋病毒亚型和菌株， 确定保护的免疫相关性。为此，我们的实验室 研究了使用猫科动物的灭活病毒疫苗方法， 免疫缺陷病毒（FIV）-艾滋病猫模型。对同源物的防护 和密切相关的FIV毒株已经用单毒株疫苗获得， 而对异源亚型的保护， 同一亚型的异源菌株一直是困难的。为了 扩大保护性免疫，来自不同亚型的FIV毒株已被 组合作为双重和三重亚型FIV疫苗的免疫原。初步 结果表明，在设定的抗原剂量下， 在保护猫免受 相同和不同亚型的异源菌株。而且 双亚型疫苗更有效地诱导合适的， 免疫猫中的可重现免疫应答， 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)活性，包括疫苗诱导的TH-1细胞因子， 干扰素-γ关于什么类型的免疫力是必要的， 艾滋病病毒的预防性保护以及 使用的系统，如静脉内与粘膜激发和体内衍生的 与体外来源的接种物相比。为了解决这些问题， 将来自接种猫的无抗体免疫细胞过继转移 免疫系统匹配的猫具有匹配免疫系统的猫 是由骨髓移植产生的在最近的初步研究中， 过继转移免疫细胞的受体被保护免受 同源FIV攻击。在这种竞争性的更新补助金，相关的 双亚型FIV疫苗诱导的保护性免疫将通过 对免疫系统匹配的猫进行过继转移研究。我们 目的是明确双亚型疫苗的细胞免疫机制 针对同源和异源亚型攻击的保护， 这种保护是否对粘膜/阴道攻击有效。

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.