COMBINED VACCINE STRATEGIES FOR THE PREVENTION OF AIDS

该计划的长期目标是开发和优化小说 针对人类的预防性免疫策略 新型重组病毒载体在免疫缺陷病毒中的应用 疫苗。NCVDG的联合计划有四个具体的 重组病毒载体疫苗。NCVDG的综合方案 有四个具体目标： 1.新型HIV和SIV疫苗的构建和生化分析， 基于活的重组痘病毒载体，活的重组腺病毒- 相关病毒载体和非传染性艾滋病毒和SIV样颗粒 源自重组痘病毒。 2.个体疫苗和疫苗的安全性和有效性比较 啮齿动物和灵长类动物的疫苗组合。 3.SIV特异性体液和免疫球蛋白的定量和定性分析 个体免疫灵长类动物的细胞免疫应答 联合疫苗。 4.分析了体液的广度、大小和自然变异 和自然感染艾滋病毒的宿主的细胞免疫反应 SIV。 该应用的新特征包括使用腺相关的 病毒(AAV)作为基因转移载体。AAV是复制缺陷的 细小病毒具有独特的特征，使其成为一种有吸引力的载体 将外来DNA稳定地输送到细胞。此外，我们还将 构建和检测新的重组痘病毒，包括鸡痘病毒 和猪瘟病毒，作为可能更安全的替代使用 牛痘病毒。重组病毒将被构建为表达 新基因的多样性。这些基因将包括临床上的基因。 来自最近患者分离株的相关HIV毒株，辅助性 除了SIV和HIV的主要抗原编码基因之外的基因，以及 包括细胞因子基因以试图增加安全性和/或 增加可用于预防母婴的疫苗 艾滋病毒的传播。SIV颗粒疫苗将在新生儿中进行研究 恒河猴的免疫原性和原代诱导细胞毒作用 淋巴细胞。类似的研究也将在HIV颗粒上进行 兔子的疫苗。这些方法中最有希望的将是 被纳入候选艾滋病毒疫苗，用于临床试验 人类。

The long-term objective of this program is to develop and optimize novel strategies for prophylactic immunization against the human immunodeficiency virus (HIV) using novel recombinant viral vector vaccines. The combined programs of this NCVDG have four specific recombinant viral vector vaccines. The combined programs of this NCVDG have four specific aims: 1. Construction and biochemical analyses of novel HIV and SIV vaccines, based on live recombinant poxvirus vectors, live recombinant adeno- associated virus vectors, and non infectious HIV and SIV-like particles derived from recombinant poxviruses. 2. Comparison of the safety and efficacy of individual vaccines and combinations of vaccines in rodents and primates. 3. Quantitative and qualitative analyses of SIV-specific humoral and cellular immune responses in primates immunized with individual or combined vaccines. 4. Analysis of the breadth, magnitude and natural variation of humoral and cellular immune responses in hosts naturally infected with HIV and SIV. Novel features of this application include the use of adeno-associated virus (AAV) as a gene transfer vector. AAV is a replication-defective parvovirus with unique features that make it attractive as a vector for the stable delivery of foreign DNA to cells. In addition, we will construct and test new recombinant poxviruses, including fowlpox virus and swinepox virus, as potentially safer alternatives to the use of vaccina virus. Recombinant viruses will be constructed expressing a variety of novel genes. Such genes will include genes from clinically relevant HIV strains derived from recent patient isolates, auxiliary genes in addition to the major antigen-encoding genes of SIV and HIV, and the inclusion of cytokine genes to attempt to increase safety and/or increase vaccine which can be used to prevent maternal-infant transmission of HIV. SIV particle vaccines will be studied in neonatal rhesus macaques for immunogenicity and primary induction of cytotoxic lymphocytes. Similar studies will be carried out with HIV particle vaccines in rabbits. The most promising of these approaches will be incorporated into candidate HIV vaccines destined for clinical trials in humans.