HIV-1 PASSIVE IMMUNITY AGAINST CORECEPTOR INTERACTIONS

描述 (改编自申请人的摘要)HIV-1涉及的分子 现在已经确定了条目，这使得有可能将此过程作为目标 抑制病毒感染的策略。这个过程需要两个分子 实体，也结合趋化因子的辅助受体和形成的复合体 在HIV-1包膜gp120和初级细胞受体cd4之间。 与共同受体相互作用中涉及的表位结合的抗体 应该中和HIV-1，因此对被动免疫有用 预防或治疗感染。在这个项目中，调查人员将使用两个 在小鼠中提高这种抗体的策略。第一个将是免疫接种 用共价交联型gp120-CD4复合体提高单克隆性 针对病毒包膜上的辅受体结合部位的抗体。这个 研究人员已经表明，这些复合体具有广泛的诱导性 中和干扰后CD4结合步骤的反应。这个 第二个是提高病毒附着部位的特异性抗体。 辅受体CCR5和CXCR4。中和阻止条目的mAbs 由该公司开发的重组DNA方法将使过程“人性化” 为被动免疫治疗提供试剂的小组。这种方法，即 允许调查人员操纵特定的免疫原，以便 获得所需的反应，将允许他们分离中和单抗 并在更短的时间内对它们进行表征 识别、描述和隔离人类对应物。

DESCRIPTION (Adapted from the applicant's abstract) The molecules involved in HIV-1 entry have now been identified making it possible to target this process for strategies to inhibit viral infection. The process requires two molecular entities, a coreceptor that also binds chemokines and a complex formed between the HIV-1 envelope, gp120, and the primary cell receptor, CD4. Antibodies that bind to epitopes involved in the coreceptor interaction should neutralize HIV-1 and therefore be useful for passive immunity to prevent or treat infection. In this project, the investigators will use two strategies to raise such antibodies in mice. The first will be immunization with covalently crosslinked gp120-CD4 complexes to raise monoclonal antibodies against the coreceptor binding site on the viral envelope. The investigators have already shown that these complexes elicit broadly neutralizing responses that interfere in a post-CD4 binding step. The second will be to raise antibodies specific for the viral attachment site on the coreceptors CCR5 and CxCR4. Neutralizing mAbs that block entry processes will be "humanized" by recombinant DNA methods developed by this group to provide reagents for passive immunotherapy. This approach, which allows the investigators to manipulate specific immunogens in order to obtain the desired responses, will allow them to isolate neutralizing mAbs from mice and to characterize them in less time than it would take to identify, characterize, and isolate the human counterparts.