HIV-1 Oligomeric Envelope-Proteoliposomes

描述（由申请人提供）：人类免疫缺陷病毒（HIV-1）是人类获得性免疫缺陷综合征（艾滋病）的主要原因。目前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接触的靶标。HIV-1包膜糖蛋白包含在病毒表面的三聚体复合体中，介导受体结合和膜融合。目前还没有设计出广泛有效的中和抗体的策略，至少部分原因是现有的免疫原不能完全模拟功能性包膜糖蛋白复合物。我们已经创建了固相蛋白脂质体，其中含有锚定在脂质膜上的三聚体HIV-1包膜糖蛋白。这项建议的具体目标是：

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.