DEVELOPMENT OF VACCINIA-BASED VACCINES FOR HIV AND SIV

开发基于痘苗的 HIV 和 SIV 疫苗

• 批准号: 3547153
• 负责人: DENNIS L PANICALI
• 金额: $ 76.05万
• 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 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3547153
• 关键词: human immunodeficiency virus; simian immunodeficiency virus; viral vaccines

The emergence of the Acquired Immunodeficiency Disease (AIDS) pandemic may represent the most serious global public health threat of the 20th century. The goal of the proposed research is the development of an efficacious vaccine against multiple strains of the Human Immunodeficiency Virus (HIV), the etiological agent of AIDS. This proposal describes the design, construction and evaluation of a series of vaccinia-based recombinant vaccines for both HIV-1 and the related Simian Immunodeficiency Virus (SIV). This will be accomplished through a coordinated program combining the talents of both academic and industrial scientists. These vaccines will express multiple HIV-1 or SIV antigens in conformations that elicit appropriate humoral and cell-mediated immune responses. Novel methods developed at AbT for rapidly generating and selecting vaccinia recombinants expressing multiple antigens are described. The nature and magnitude of the humoral and cell mediated immune responses elicited by the recombinant viruses will be evaluated in both murine and non-human primate systems. In addition, histocompatible human target cells infected with the recombinant viruses will be used to assess, in vitro, cytotoxic cellular responses of HIV-1 infected individuals to the vaccinia-expressed HIV-1 antigens. These in vitro studies will help define the HIV-1/SIV antigens and /or antigenic epitopes most appropriate for inclusion into a potential vaccine. The demonstration of the efficacy of an HIV-1 vaccine is hampered by the lack of the induction of an acquired immunodeficiency syndrome in HIV-1 infected non-human primates. The development of an AIDS- like syndrome in macaques following infection with SIV allows the evaluation of the efficacy of potential vaccines in a primate model. This system will permit characterization of the immune responses induced and the protection afforded by vaccinia recombinants expressing combinations of SIV antigens. The information derived from these combined HIV-1 and SIV studies will be elaborated to produce safe and efficacious vaccinia-based HIV- 1 vaccines for use in humans.

获得性免疫缺陷病（艾滋病）的出现 大流行可能是最严重的全球公共卫生威胁 20世纪。 拟议研究的目标是 开发针对多种病毒株的有效疫苗 人类免疫缺陷病毒 (HIV)，其病原体 艾滋病。 该提案描述了设计、施工和 一系列基于痘苗的重组疫苗的评估 HIV-1 和相关的猿猴免疫缺陷病毒 (SIV)。 这将通过一个协调计划来完成，该计划结合了 学术和工业科学家的才能。 这些 疫苗将在体内表达多种 HIV-1 或 SIV 抗原 引发适当的体液和细胞介导的构象 免疫反应。 AbT 开发的新方法可快速 产生并选择表达多种的痘苗重组体 描述了抗原。 体液的性质和程度 以及重组体引发的细胞介导的免疫反应 病毒将在鼠类和非人类灵长类动物中进行评估 系统。 此外，组织相容性人类靶细胞感染 重组病毒将用于体外评估， HIV-1感染者对病毒的细胞毒性细胞反应 牛痘表达的 HIV-1 抗原。 这些体外研究将 最有助于定义 HIV-1/SIV 抗原和/或抗原表位 适合纳入潜在的疫苗中。 这 HIV-1 疫苗功效的证明受到以下因素的阻碍 缺乏诱导获得性免疫缺陷综合征 在 HIV-1 感染的非人类灵长类动物中。 艾滋病的发展—— 猕猴感染 SIV 后出现类似综合症， 评估潜在疫苗在灵长类动物中的功效 模型。 该系统将允许表征免疫 痘苗引起的反应和提供的保护 表达SIV抗原组合的重组体。 这 从这些 HIV-1 和 SIV 综合研究中获得的信息将 精心设计以生产安全有效的基于痘苗的艾滋病毒 1 用于人类的疫苗。