COMBINED VACCINE STRATEGIES FOR THE PREVENTION OF AIDS

该计划的长期目标是开发和优化新的 针对人类的预防性免疫策略 使用新重组病毒载体的免疫缺陷病毒（HIV） 疫苗。 该NCVDG的组合方案有四个具体的 重组病毒载体疫苗。 该NCVDG的组合程序 有四个具体目标： 1.新型HIV和SIV疫苗的构建和生化分析， 基于活重组痘病毒载体，活重组腺病毒， 相关病毒载体和非感染性HIV和SIV样颗粒 来源于重组痘病毒。 2. 比较各种疫苗的安全性和有效性， 在啮齿动物和灵长类动物中的疫苗组合。 3. SIV特异性体液免疫和细胞免疫的定量和定性分析 在用单独或单独免疫的灵长类动物中的细胞免疫应答， 联合疫苗。 4. 体液免疫的广度、强度和自然变异分析 和自然感染HIV的宿主的细胞免疫反应， SIV 本申请的新特征包括使用腺相关病毒载体。 病毒（AAV）作为基因转移载体。 AAV是一种复制缺陷型 细小病毒具有独特的功能，使其作为一种载体有吸引力， 将外源DNA稳定地输送到细胞中。 此外，我们将 构建和测试新的重组痘病毒，包括鸡痘病毒 和猪痘病毒，作为使用 牛痘病毒 重组病毒将被构建成表达一种 各种新基因。 这些基因将包括来自临床的基因。 来自近期患者分离株的相关HIV毒株，辅助 除了SIV和HIV的主要抗原编码基因之外的基因，和 包括细胞因子基因以试图增加安全性和/或 一种可用于预防母婴传播增苗 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细胞毒性的初级诱导 淋巴细胞 类似的研究将用艾滋病毒颗粒进行 兔子的疫苗 这些方法中最有前途的是 纳入到预定用于临床试验的候选艾滋病毒疫苗中， 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.