PEPTIDE MIMICS OF NEUTRALIZING SITES ON HIV ENV PROTEINS

描述：(改编自申请者摘要)：人类感染 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感染者产生的抗体 中和广泛的HIV-1毒株。这些产品主要是由 长期不进步的人；感染了多年的人，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gp20， Gp41及其前体gp60；已经有三种这样的人类抗体 克隆、BL2、2F5和2G12。相比之下，大多数人产生的抗体 HIV-1感染者(包括针对信封的抗体 蛋白质)不会杀死病毒或来自不同来源的病毒感染细胞 HIV-1毒株。 申请者提议寻找针对HIV-1感染的疫苗的线索 这将诱导产生中和抗体，以对抗广泛的 HIV-1毒株的谱系。他们将使用克隆的HIV-1中和 抗体BL2、2F5和2G12筛选一组15-20个多肽文库。 面板中的每个库包含2亿到10亿个不同的 分子，每个文库中的多肽具有不同的主导作用 形状。因此，申请者将搜索大量的序列和 寻找与HIV-1中和抗体结合的多肽的结构。 他们将测试这些多肽是否能够诱导产生 通过若干免疫策略产生艾滋病毒-1交叉反应抗体，以及 然后检测免疫血清中是否存在HIV-1结合抗体 用于中和活性。在接种疫苗的同时，申请者 将使用其模拟表位为 在结构上有很好的特点。这将允许申请者评估 他们在结构层面上的免疫战略。申请者还将 评估这些肽是否具有预测HIV-1感染的能力 人类已经制造出类似于中和单抗的抗体 抗体。根据这一点，申请者将决定是否类似 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.