An Envelope Containing HIV Pseudovirion Vaccine

装有 HIV 伪病毒疫苗的信封

基本信息

批准号：
6496153
负责人：
Kathie Grovit-Ferbas
金额：
$ 18.57万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2007-04-30
项目状态：
已结题

项目摘要

DESCRIPTION: (Provided by Applicant) This proposal represents a multi-disciplinary approach to develop an envelope-containing heat-treated pseudovirion vaccine using novel applications of classical viral vaccine technologies. Our overall hypothesis is that an envelope-containing heat-treated pseudovirion could serve as the basis for a safe and effective HIV vaccine. Data from ongoing vaccine trials indicate that a preventive HIV vaccine is going to need to elicit broad-based immune responses. DNA and vector-based vaccines have been successful at inducing T cell responses, but these appear to be insufficient to provide protection from infection. Relevant neutralizing antibodies can offer protection from infection if they are present in sufficient concentrations at the time of infection. Unfortunately, attempts to induce potent neutralizing antibody responses with recombinant monomeric subunit vaccines have generally been unsuccessful. This limited success suggests that a vaccine will likely need to mimic or improve upon the native envelope structure. Taken together, it is crucial to explore vaccine strategies capable of eliciting potent antibody responses to be used alone, or in conjunction with vaccines that target cellular responses. The use of whole virions provides a complex antigen with close to native conformation and is one approach which could be taken to develop a safe and effective HIV-1 vaccine. An envelope-containing heat-treated pseudovirion has a theoretical advantage over a whole killed vaccine since it would consist of a complex mixture of immunogenic viral antigens, but could be engineered to be defective in regions important for infectivity, as well as in regions that serve as potential decoys for potent immune responses. More importantly, we have developed procedures which result in enhanced antigenicity of oligomeric envelope structures on whole virions which can be easily adapted to envelope-containing pseudovirions. Our Specific Aims are: Aim 1: To test the hypothesis that an envelope-containing pseudovirion will demonstrate enhanced antigenicity following heat treatment in a manner analogous to a heat-treated whole virion. Aim 2: To test the hypothesis that vaccination with an envelope-containing heat-treated pseudovirion can result in the induction of potent neutralizing antibodies in a small animal model. Aim 3: To test the hypothesis that vaccination with an envelope-containing heat-treated pseudovirion can result in the induction of humoral and cellular immune responses generally regarded as protective in non human primates. Aim 4: To test the hypothesis that an envelope-containing heat-treated pseudovirion can protect rhesus macaques against infection with a heterologous SHIV.

描述：（由申请人提供）该提案代表多学科的方法来开发富含信封的热处理使用经典病毒疫苗的新型应用疫苗疫苗技术。我们的总体假设是一个含信封的热处理的伪旋转可以作为安全有效的艾滋病毒的基础疫苗。正在进行的疫苗试验中的数据表明预防性艾滋病毒疫苗将需要引起广泛的免疫反应。 DNA和基于向量的疫苗已经成功诱导T细胞反应，但是这些似乎不足以提供免受感染的保护。相关的中和抗体如果存在，可以保护免受感染的保护感染时足够浓度。不幸的是，尝试用重组单体诱导有效的中和抗体反应亚基疫苗通常没有成功。这个有限的成功表明疫苗可能需要模仿或改善本地信封结构。综上所述，探索疫苗策略至关重要能够单独使用有效抗体反应，或者与靶向细胞反应的疫苗结合。整体的使用 Virions提供了一种具有接近天然构象的复杂抗原，是一个可以采用开发安全有效的HIV-1疫苗的方法。一个富含信封的热处理伪动物在理论上优势整个疫苗，因为它将由复杂的混合物组成免疫原性病毒抗原，但可以设计为在区域中有缺陷对于感染力以及作为潜在诱饵的地区重要用于有效的免疫反应。更重要的是，我们已经开发了程序这导致寡聚包膜结构的抗原性增强可以容易适应含有信封的伪动仪的整个病毒体。我们的具体目的是：目的1：检验以下假设：含有信封的伪文化以某种方式证明热处理后的抗原性增强类似于热处理的整个病毒体。目标2：检验以包膜接种疫苗接种的假设热处理的假期可能导致有效中和小动物模型中的抗体。目标3：测试以包膜疫苗接种的假设热处理假循环会导致体液和细胞的诱导免疫反应在非人类灵长类动物中通常被视为保护性。目标4：检验含有信封的热处理的假设伪造可以保护恒河猕猴免受异源感染湿婆。