NOVEL ROUTES TO NATIVE OLIGOMERIC HIV1 ENVELOPE

描述：亚单位疫苗制剂失败的原因之一是 它们不能有效地呈现天然包膜表位。 免疫原 例如 HIV gp160 实际上代表病毒包膜的非天然形式 （病毒碎片）。 gp160 前体的丰度可能 蛋白质甚至干扰对天然反应的成熟 包膜本身是一种较差的免疫原。 如果一个新颖的策略可以 开发以获得包膜免疫原来刺激强 针对天然包膜的抗体反应和对病毒的反应降低 碎片，对 hu-PBL-SCID 小鼠的 HIV-1 的保护是可以实现的。 有 4 个具体目标： 1) 定义基于信封的质量 免疫原使用一组单克隆抗体来区分 天然病毒颗粒相关的 gp120 和非天然病毒碎片 gp160。 2) 至 改进 gp160 前体的体外处理，以及 3) 分割大分子 细胞表面天然构型的包膜量或 假病毒体。 4) 将中和抗血清转移到 hu-PBL-SCID 小鼠中 为了评估体内对 HIV-1 的保护作用。

DESCRIPTION: One reason for the failure of subunit vaccine preparations is that they do not present native envelope epitopes efficiently. Immunogens such as HIV gp160 actually represent nonnative forms of the viral envelope (viral debris). It is possible that the abundance of the gp160 precursor protein even interferes with the maturation of the response to native envelope, which itself is a poor immunogen. If a novel strategy can be developed to obtain envelope immunogens targeted to stimulate a strong antibody response against native envelope and a decreased response to viral debris, protection against HIV-1 in hu-PBL-SCID mice would be achievable. There are 4 specific aims: 1) To define the quality of envelope-based immunogen using a set of monoclonal antibodies that distinguish between the native virion-associated gp120 and the nonnative viral debris gp160. 2) To improve processing of gp160 precursor in vitro and 3) to partition a large amount of envelope in its native configuration on the surface of cells or pseudovirions. 4) To transfer neutralizing antisera in hu-PBL-SCID mice in order to assess protection against HIV-1 in vivo.