NOVEL, LIVE, RECOMBINANT YEAST BASED HIV VACCINE

描述（改编自申请人摘要）：细胞毒性T细胞 （CTL）介导的免疫被认为在减少病毒感染中起主要作用。 艾滋病病毒感染的早期负荷，并在减缓艾滋病的进展速度。 目前的大多数HIV疫苗，由HIV衍生蛋白或 杀死病毒，引发强烈的抗体反应，但在诱导 CTL介导的免疫。 研究人员开发了一种新的艾滋病毒 疫苗递送系统（HIVAX），其由活的、重组的 表达gp 16 O蛋白的酿酒酵母， 抗原特异性辅助细胞和细胞毒性T细胞活性。 重要 拟议疫苗的特点是：（i）不含 （ii）不需要佐剂;（iii）刺激两者 细胞介导的和体液免疫;（iv）可以是口服活性的;和（v）可以 使用重组DNA技术容易地工程化以表达三种或更多种蛋白质， 更多蛋白质抗原 本提案的具体目的是：（1） 进行比较研究时，HIVAX引起的免疫类型， 通过全身或粘膜途径在小鼠中施用。 这项工作将 确定最有效的疫苗接种途径和剂量， 未来的临床前和临床试验;（2）研究 CTL活性的HIVAX诱导。 辅助性T细胞的作用，抗原 通过II类主要组织相容性复合体（MHC）分子呈递， 和巨噬细胞通过I类MHC分子呈递HIVAX抗原 在CTL介导的免疫中，将进行评估。 这 这些信息对于阐明疫苗如何起作用至关重要， 导致疫苗的改进版本;（3）确定生物学 疫苗在小鼠中引发保护性免疫的效力。 肿瘤 将通过测试肿瘤细胞是否表达 gp 160不能在接种小鼠中建立肿瘤。

DESCRIPTION (adapted from applicant's abstract): Cytotoxic T cell (CTL)-mediated immunity is considered to play a major role in reducing viral load early in HIV infection, and in slowing the rate of progression to AIDS. Most of the current HIV vaccines, consisting of HIV-derived proteins or killed virus, elicit strong antibody responses but are poor at inducing CTL-mediated immunity. The investigators have developed a novel, HIV vaccine delivery system (HIVAX) consisting of live, recombinant Saccharomyces cerevisiae expressing the gp16O protein, that elicits antigen-specific helper and cytotoxic T cell activity. The important characteristics of the proposed vaccine are that it: (i) contains no infectious material; (ii) does not require adjuvants; (iii) stimulates both cell-mediated and humoral immunity; (iv) may be orally active; and (v) can be readily engineered using recombinant DNA technology to express three or more protein antigens. The specific aims of this proposal are: (1) to perform a comparative study of the types of immunity elicited when HIVAX is administered by systemic or mucosal routes in mice. This work will establish the most efficient routes and dosage of vaccine application for future pre-clinical and clinical trials; (2) to investigate the mechanism of HIVAX induction of CTL activity. The role of helper T cells, antigen presentation via class II major histocompatibility complex (MHC) molecules, and macrophage presentation of the HIVAX antigens via class I MHC molecules in CTL mediated immunity, will be assessed. This information will be critical for elucidating how the vaccine works and may lead to improved versions of the vaccine; and (3) to determine biological efficacy of the vaccine for eliciting protective immunity in mice. A tumor vaccine model will be investigated by testing whether tumor cells expressing gp 160 fail to establish tumors in vaccinated mice.