DEVELOPMENT OF VACCINIA-BASED VACCINES FOR HIV AND SIV

获得性免疫缺陷病(AIDS)的出现 大流行可能是最严重的全球公共卫生威胁 20世纪的历史。拟议研究的目标是 多毒株高效疫苗的研制 人类免疫缺陷病毒(HIV)，其病原体是 艾滋病。本建议书介绍了该方案的设计、施工和 一系列牛痘重组疫苗的免疫效果评价 HIV-1和相关的猿猴免疫缺陷病毒(SIV)。 这将通过一个协调的计划组合来实现 学术和工业科学家的才华。这些 疫苗将表达多种HIV-1或SIV抗原 诱导适当的体液和细胞介导的构象 免疫反应。ABT开发的新方法用于快速 重组痘苗病毒表达载体的产生和筛选 对抗原进行了描述。幽默的性质和程度 和细胞介导的免疫应答的重组 病毒将在小鼠和非人类灵长类动物身上进行评估 系统。此外，组织相容的人类靶细胞感染 重组病毒将被用于在体外评估， HIV-1感染者对病毒的细胞毒作用 痘苗病毒表达的HIV-1抗原。这些体外研究将 帮助确定HIV-1/SIV抗原和/或抗原表位 适合纳入潜在疫苗。这个 HIV-1疫苗有效性的演示受到以下因素的阻碍 缺乏对获得性免疫缺陷综合征的诱导 在感染了HIV-1的非人类灵长类动物中。一种艾滋病的发展-- 感染SIV后猕猴出现的类似综合症允许 潜在疫苗在灵长类动物中的效力评估 模特。这个系统将允许对免疫系统进行表征 牛痘引起的反应和提供的保护 表达SIV抗原组合的重组体。这个 从这些HIV-1和SIV联合研究中获得的信息将 以生产安全有效的牛痘为基础的艾滋病毒- 1用于人类的疫苗。

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.