ISS AS AN ADJUVANT FOR SIV/HIV-BASED VACCINE

ISS 作为 SIV/HIV 疫苗的佐剂

• 批准号: 6080803
• 负责人: Eyal Raz
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6080803
• 关键词: AIDS vaccines; CpG islands; Macaca; active immunization; bacterial DNA; human immunodeficiency virus; immunity; immunomodulators; laboratory mouse; nucleic acid sequence; oligonucleotides; simian immunodeficiency virus; vaccine development

DESCRIPTION: (Adapted from Applicant's Abstract) The development of an HIV vaccine has been slow, and successes in various models including human trials have been limited. A candidate vaccine that can induce broadly neutralizing antibodies, systemic Th1 and CTL responses as well as mucosal IgA and CTL responses, represents a logical and required developmental strategy. Our preliminary data generated in various mouse models and in primates suggest that certain bacterial DNA sequences (ISS or CpG motif) provide the necessary adjuvanticity and immunomodulatory properties to address this requirement. Hence, ISS-based vaccines (conjugated or co-injected with an antigen) can generate a state of "global immunity"; i.e., humoral and cellular, systemic and mucosal immune responses in an antigen-specific fashion. We therefore propose to 1) investigate this further with readily available SIV dead, inactivated viral particles in the mouse to better define the immunological basis for our encouraging observations, and to define and optimize the best parameters to study ISS-SIV/HIV-based immunization in the macaque model; 2) characterize the immune response to ISS-based vaccine in an immune deficient mouse, which emulates AIDS patients; and 3) evaluate ISS-based HIV vaccines in the macaque for their ability to induce specific immune responses and to protect from lethal HIV/SIV challenge. We hope that the data generated in this study will help in the design of a protective vaccination strategy against HIV in humans.

描述：（改编自申请人的摘要）艾滋病毒的发展 疫苗一直很慢，并且在包括人类试验在内的各种模型中取得了成功 受到限制。可以广泛中和的候选疫苗 抗体，系统性TH1和CTL响应以及粘膜IGA和CTL 反应，代表一种逻辑且必需的发展策略。我们的 在各种鼠标模型和灵长类动物中生成的初步数据表明 某些细菌DNA序列（ISS或CPG基序）提供必要的 辅助性和免疫调节特性以满足此要求。 因此，基于ISS的疫苗（与抗原共轭或共轭）可以 产生“全球免疫力”的状态；即体液和细胞，全身和 粘膜免疫反应以抗原特异性的方式。因此，我们提出 到1）进一步调查此事，可随时可用的SIV死亡，灭活 小鼠中的病毒颗粒以更好地定义我们的免疫学基础 鼓励观察，并定义和优化最佳参数 猕猴模型中基于ISSIV/HIV的研究； 2）表征 免疫反应在免疫缺陷小鼠中基于ISS的疫苗，该疫苗 模拟艾滋病患者； 3）评估猕猴中基于ISS的HIV疫苗 因为他们能够诱导特定免疫反应并保护 致命的HIV/SIV挑战。我们希望本研究中产生的数据将 帮助设计针对人类艾滋病毒的保护性疫苗接种策略。