Protective CMI Mechanism of a Dual-subtype FIV Vaccine

双亚型FIV疫苗的保护性CMI机制

• 批准号: 6845668
• 负责人: Janet K. Yamamoto
• 金额: $ 36.38万
• 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 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845668
• 关键词: B lymphocyte; cats; cellular immunity; cytotoxic T lymphocyte; feline immunodeficiency virus; helper T lymphocyte; mucosal immunity; passive immunization; tissue /cell culture; vaccine development; viral vaccines

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.

描述：（改编自申请人的摘要） 艾滋病毒疫苗的开发一直在确定一种预防性策略 为越来越多的艾滋病毒亚型和菌株提供保护 确定保护的免疫相关性。为此，我们的实验室 已经使用猫科研究了灭活的病毒疫苗方法 AIDS的免疫缺陷病毒（FIV）-CAT模型。防止同源 单元疫苗已经达到了密切相关的FIV菌株， 而对异源亚型的保护，甚至明显 同一亚型的异源菌株很困难。为了 扩大保护性免疫力，来自不同亚型的FIV菌株已经 将双重和三重型FIV疫苗的免疫原混合在一起。初步的 结果表明，在固定的抗原剂量下，三重含量疫苗为 在保护猫免受的双重含量疫苗中不如双含量疫苗有效 相同和不同亚型的异源菌株。此外， 双重型疫苗在引起适当的疫苗方面更有效， 疫苗接种猫中可重复的免疫反应，检测到 病毒中和抗体，细胞毒性t膜细胞活性和T助血器 （TH）包括疫苗诱导的Th-I细胞因子，例如 干扰素伽马。关于什么类型的免疫力是必不可少的争议 预防性保护艾滋病病毒和挑战类型 使用的系统，例如静脉内与粘膜挑战和体内衍生的系统 与体外衍生的接种物相对于。为了解决这些问题， 接种猫的无抗体免疫细胞将被转移 到具有匹配的免疫系统的猫。具有匹配免疫系统的猫是 由骨髓移植开发。在最近的初步研究中 保护免疫细胞的受体受到保护 同源FIV挑战。在这种竞争性更新赠款中， 双重型FIV疫苗引起的保护性免疫力将由 对具有匹配的免疫系统的猫进行收养转移研究。我们的 目的是确定双含量疫苗的细胞免疫机制 防止同源和异源亚型挑战并进行测试 这种保护是否有效抵抗粘膜/阴道挑战。