NOVEL, LIVE, RECOMBINANT YEAST BASED HIV VACCINE

描述(摘自申请者摘要)：细胞毒性T细胞 细胞毒性T淋巴细胞(CTL)介导的免疫被认为在减少病毒感染方面发挥了重要作用 在艾滋病毒感染的早期加载，并减缓向艾滋病的进展速度。 目前大多数艾滋病毒疫苗都是由艾滋病毒衍生蛋白或 杀死病毒，引发强烈的抗体反应，但诱导能力较差 CTL介导的免疫。研究人员开发了一种新型的艾滋病毒 疫苗递送系统(HIVAX)由活的、重组的 表达gp16O蛋白的酿酒酵母 抗原特异性辅助性T细胞和细胞毒T细胞活性。重要的是 拟议疫苗的特点是：(I)不含 感染性物质；(Ii)不需要佐剂；(Iii)刺激两者 细胞介导的免疫和体液免疫；(Iv)可以是口头主动的；和(V)可以 很容易利用重组DNA技术来表达三个或三个或 更多的蛋白质抗原。这项建议的具体目的是：(1) 对HIVAX感染后产生的免疫类型进行比较研究 在小鼠体内通过全身或粘膜途径给药。这项工作将 建立最有效的疫苗应用途径和剂量 未来的临床前和临床试验；(2)探讨丹参的作用机制 HIVAX诱导CTL活性。辅助性T细胞、抗原的作用 通过第二类主要组织相容性复合体(MHC)分子递呈， HIVAX抗原通过I类MHC分子和巨噬细胞递呈 在CTL介导的免疫中，将被评估。这 信息将对阐明疫苗的作用方式至关重要，并可能 导致改进的疫苗版本；以及(3)确定生物学上的 该疫苗对小鼠产生保护性免疫的效果。肿瘤 疫苗模型将通过测试肿瘤细胞是否表达 GP 160未能在接种疫苗的小鼠中建立肿瘤。

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.