HIV-1 Oligomeric Envelope-Proteoliposomes

描述(申请人提供)：人类免疫缺陷病毒(HIV-1)是人类获得性免疫缺陷综合征(AIDS)的主要原因。迫切需要一种预防性疫苗来遏制艾滋病毒-1大流行。通过HIV-1疫苗激发病毒中和抗体将是可取的。HIV-1包膜糖蛋白gp120和gp41是病毒粒子上唯一可被中和抗体访问的靶标。HIV-1包膜糖蛋白以三聚体形式存在于病毒表面，介导受体结合和膜融合。诱导广泛有效的中和抗体的策略尚未制定，至少部分原因是现有的免疫原不能完美地模拟功能性包膜糖蛋白复合体。我们已经创建了含有三聚体HIV-1包膜糖蛋白的固相蛋白脂质体，这些蛋白被固定在脂膜中。这项建议的具体目标是： 1)创建含有包膜糖蛋白的蛋白质脂质体，有效地模拟HIV-1包膜复合体的功能； 2)利用包膜蛋白脂质体从噬菌体展示文库中筛选新的寡聚体特异性配体； 3)评价包膜蛋白脂质体的免疫原性。

DESCRIPTION (provided by applicant): Human immunodeficiency virus (HIV-1) is the major cause of acquired immunodeficiency syndrome (AIDS) in humans. A prophylactic vaccine is urgently needed to curb the HIV-1 pandemic. The elicitation of virus-neutralizing antibodies by an HIV-1 vaccine would be desirable. The HIV-1 envelope glycoproteins, gp120 and gp41, are the only targets on the virion accessible to neutralizing antibodies. The HIV-1 envelope glycoproteins are contained in trimeric complexes on the viral surface, and mediate receptor binding and membrane fusion. Strategies for eliciting broadly effective neutralizing antibodies have yet to be devised, at least in part because the available immunogens imperfectly mimic the functional envelope glycoprotein complex. We have created solid-phase proteoliposomes containing trimeric HIV-1 envelope glycoproteins anchored in a lipid membrane. The specific aims of this proposal are: 1) To create proteoliposomes containing envelope glycoproteins that effectively mimic the functional HIV-1 envelope complex; 2) To use the Env-proteoliposomes to select novel oligomer-specific ligands from phage-display libraries; and 3) To evaluate the immunogenicity of Env-proteoliposomes.