PEPTIDE MIMICS OF NEUTRALIZING SITES ON HIV ENV PROTEINS

描述：（改编自申请人摘要）：人感染 免疫缺陷病毒1型（HIV-1）导致获得性免疫缺陷 综合症（艾滋病）。 只有少数HIV-1感染者产生抗体， 中和多种HIV-1病毒株。 这些主要由 长期无进展者;多年感染的人，但 从未出现过艾滋病的症状和体征。 这些中和 抗体主要针对病毒的包膜蛋白，gp 120， gp 41和它们的前体gp 160;三种这样的人抗体已经被 克隆，bl 2，2F 5和2G 12。 相反，大多数人产生的抗体 HIV-1感染者（包括抗包膜抗体） 蛋白质）不杀死病毒或病毒感染的细胞， HIV-1病毒株。 申请人建议寻找预防HIV-1感染的疫苗的线索 这将诱导产生中和抗体， HIV-1病毒谱。 他们将使用单克隆抗体， 抗体b12、2F 5和2G 12以筛选一组15-20个肽文库。 面板中的每个库包含2亿到10亿个不同的 分子，并且每个文库中的肽具有不同的主导结构。 形状 因此，申请人将搜索各种各样的序列， 结构，以寻找结合HIV-1中和抗体的肽。 他们将测试这些肽诱导产生 HIV-1交叉反应性抗体通过一些免疫策略， 然后将测试免疫血清中是否存在HIV-1结合抗体， 用于中和活性。 沿着这些免疫接种， 将使用肽进行免疫，肽的模拟表位是 结构特征良好。 这将允许申请人评估 在结构层面上的免疫战略。 申请人还将 评估这些肽预测HIV-1感染者 一个人已经制造了类似于中和单克隆抗体的抗体， 抗体的 由此，申请人将确定是否类似 中和抗体是由不同的人制造的。

DESCRIPTION: (Adapted from applicant's abstract): Infection with the human immunodeficiency virus type1 (HIV-1) leads to the acquired immunodeficiency syndrome (AIDS). Only a few HIV-1-infected people produce antibodies that neutralize a broad range of HIV-1 strains. These are mainly produced by long-term non-progressers; people, who have been infected for years, but have never developed the signs and symptoms of AIDS. These neutralizing antibodies are mostly against the envelope proteins of the virus, gpl20, gp41 and their precursor gpl60; three such human antibodies have been cloned, bl2, 2F5 and 2G12. In contrast, the antibodies produced by most HIV-1-infected people (which include antibodies against the envelope proteins) do not kill the virus or virus-infected cells from different strains of HIV-1. The applicants propose to find leads for a vaccine against HIV-1 infection that would induce the production of neutralizing antibodies against a broad spectrum of HIV-1 strains. They will use the monoclonal, HIV-1-neutralizing antibodies bl2, 2F5 and 2G12 to screen a panel of 15-20 peptide libraries. Each library in the panel contains 200-million to 1-billion different molecules, and the peptides in each library have a different predominating shape. Thus, the applicants will search a large variety of sequences and structures to find peptides that bind neutralizing antibodies to HIV-1. They will test these peptides for their ability to induce the production of HIV-1-cross-reactive antibodies by a number of immunization strategies, and will then test immune sera for the presence of HIV-1-binding antibodies and for neutralizing activity. Along with these immunizations, the applicants will perform immunizations using peptides whose mimicked epitopes are structurally well characterized. This will allow the applicants to assess their immunization strategy on a structural level. The applicants will also assess the peptides for their ability to predict whether an HIV-1-infected person has made antibodies that are similar to the neutralizing monoclonal antibodies. From this, the applicants will determine whether similar neutralizing antibodies are made by different people.