COMBINED VACCINE STRATEGIES FOR THE PREVENTION OF AIDS

预防艾滋病的联合疫苗策略

• 批准号: 2063386
• 负责人: DENNIS L PANICALI
• 金额: $ 114.28万
• 依托单位: THERION BIOLOGICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2063386
• 关键词: AIDS vaccines; human immunodeficiency virus; simian immunodeficiency virus; viral vaccines

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.

该计划的长期目标是开发和优化新颖的 针对人类的预防性免疫策略 使用新型重组病毒载体的免疫缺陷病毒（HIV） 疫苗。 该 NCVDG 的综合计划有四个具体内容 重组病毒载体疫苗。 本次 NCVDG 的综合项目 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、活重组腺病毒载体 相关病毒载体以及非传染性 HIV 和 SIV 样颗粒 源自重组痘病毒。 2. 个别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特异性体液的定量和定性分析 灵长类动物的细胞免疫反应 联合疫苗。 4. 体液的广度、幅度和自然变异分析 和自然感染艾滋病毒的宿主的细胞免疫反应 SIV。 该应用程序的新颖功能包括使用腺相关 病毒（AAV）作为基因转移载体。 AAV 是一种复制缺陷型病毒 细小病毒具有独特的特征，使其作为载体具有吸引力 将外源 DNA 稳定输送至细胞。 此外，我们将 构建并测试新的重组痘病毒，包括禽痘病毒 和猪痘病毒，作为使用的潜在更安全的替代品 疫苗病毒。 重组病毒将被构建表达 各种新颖的基因。 这些基因将包括来自临床的基因 来自最近患者分离株的相关 HIV 毒株，辅助 除了 SIV 和 HIV 的主要抗原编码基因之外的基因，以及 包含细胞因子基因以试图提高安全性和/或 增加可用于母婴预防的疫苗 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细胞毒性的初级诱导 淋巴细胞。 类似的研究也将针对 HIV 颗粒进行 兔子疫苗。 这些方法中最有前途的是 纳入用于临床试验的候选艾滋病毒疫苗 人类。