NOVEL ROUTES TO NATIVE OLIGOMERIC HIV1 ENVELOPE

描述：亚单位疫苗制备失败的原因之一是 它们不能有效地呈现天然的包膜表位。免疫原 例如HIV gp160实际上代表了病毒包膜的非本地形式 (病毒碎片)。有可能gp160前体的丰度 蛋白质甚至干扰对天然免疫反应的成熟。 信封本身就是一种很差的免疫原。如果一种新的战略可以 开发的目的是获得靶向刺激的包膜免疫原强 对天然包膜的抗体反应和对病毒的反应降低 如果有了病毒碎片，在Hu-PBL-SCID小鼠中预防HIV-1将是可以实现的。 有4个具体目标：1)定义基于信封的质量 使用一组单抗来区分 天然病毒粒子相关的gp120和非天然病毒碎片gp160。2)至 改进gp160前体的体外加工工艺和3)分离大的 细胞表面上原始构型的包裹量或 假病毒粒子。4)将Hu-PBL-SCID小鼠的中和抗血清转移到 以评估体内对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.