DEVELOPMENT OF VACCINIA-BASED VACCINES FOR HIV AND SIV

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世纪的最高纪录 拟议研究的目标是 开发针对多个菌株的有效疫苗 人类免疫缺陷病毒（HIV）， 艾滋病 本建议书描述了设计、施工和 一系列牛痘重组疫苗的评价 HIV-1和相关的猿猴免疫缺陷病毒（SIV）。 这将通过一个协调的方案来实现， 学术和工业科学家的才能。 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开发的快速创新方法 产生和选择表达多个 描述了抗原。 体液免疫的性质和程度 和由重组体引起的细胞介导的免疫应答 将在鼠和非人灵长类动物中评价病毒 系统. 此外，组织相容性人类靶细胞感染 与重组病毒将被用来评估，在体外， HIV-1感染者对抗HIV-1抗体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 有助于确定HIV-1/SIV抗原和/或抗原表位 适合于包含在潜在的疫苗中。 的 HIV-1疫苗有效性的证明受到以下因素的阻碍： 缺乏对获得性免疫缺陷综合症的诱导 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后出现的类SIV综合征 在灵长类动物中评价潜在疫苗的效力 模型 该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。 的 从这些HIV-1和SIV联合研究中获得的信息将 以生产安全有效的基于疫苗的HIV- 1疫苗用于人类。

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.