DEVELOPMENT OF A NOVEL MULTIENVELOPE AIDS VACCINE

新型多包膜艾滋病疫苗的开发

• 批准号: 6609791
• 负责人: JULIA L HURWITZ
• 金额: $ 119.12万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-15 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6609791
• 关键词: AIDS; AIDS vaccines; HIV envelope protein; human immunodeficiency virus 1; vaccine development

St. Jude Children's Research Hospital (SJCRH) initiated an HIV-1 vaccine program five years ago with the conviction that his complex issue would be most effectively addressed through a coordinated, multi-disciplinary approach; the program thus currently involves investigators from SJCRH departments of Immunology , Virology, Infectious Diseases and Structural Biology. The central problem in developing an effective HIV-1 vaccine lies in the antigenic diversity of the virus. The SJCRH HIV-1 vaccine program is unique in explicitly acknowledging this antigenic complexity, by matching the diversity of the pathogen with a diversity of vaccine structures. Thus far, work within the program has resulted in the initiation of an FDA-approved, phase I clinical trial of PolyEnv1, the first HIV vaccine to encompass more than one or two HIV envelope protein structures. The ongoing clinical trial with PolyEnv1 has employed an attenuated live virus vehicle to deliver the vaccine. Preliminary data indicate that modification of the vaccination regime to deliver the cocktail of envelope protein structures represented in PolyEnv1 in a sequential combination of three different immunogenic forms (DNA, attenuated virus and native protein) may result in the generation of neutralizing antibodies at a much increased titer. Specific Aims in Projects 1 (P. Doherty) and 2 (R. Webster) use mouse models to explore the nature of the immune response to combinations of immunogenic forms, to optimize vaccination schemes and to determine the relationship between immunogen complexity and vaccine efficiency. Project 3 (J. Hurwitz) implements the findings of Projects 1 and 2 in a primate (macaques) model of vaccination against immunodeficiency virus infection, as well as developing optimal vaccine manufacturing schemes. Project 4 (K. Slobod) builds on these studies, initiating clinical trials of the safety and effectiveness of vaccines comprised of combinations of immunogenic envelopes.

圣裘德儿童研究医院 (SJCRH) 五年前启动了 HIV-1 疫苗计划，坚信通过协调一致的多学科方法可以最有效地解决他的复杂问题；因此，该计划目前涉及来自 SJCRH 免疫学、病毒学、传染病和结构生物学部门的研究人员。开发有效的 HIV-1 疫苗的核心问题在于病毒的抗原多样性。 SJCRH HIV-1 疫苗计划的独特之处在于，通过将病原体的多样性与疫苗结构的多样性相匹配，明确承认了这种抗原的复杂性。到目前为止，该计划的工作已启动了 FDA 批准的 PolyEnv1 的 I 期临床试验，这是第一种包含超过一个或两个 HIV 包膜蛋白结构的 HIV 疫苗。正在进行的 PolyEnv1 临床试验采用了减毒活病毒载体来提供疫苗。初步数据表明，对疫苗接种方案进行修改，以三种不同免疫原性形式（DNA、减毒病毒和天然蛋白）的顺序组合来递送以 PolyEnv1 为代表的包膜蛋白结构混合物，可能会导致中和抗体的产生量大大增加。效价。项目 1 (P. Doherty) 和 2 (R. Webster) 的具体目标使用小鼠模型来探索对免疫原形式组合的免疫反应的性质，优化疫苗接种方案并确定免疫原复杂性和疫苗效率之间的关系。项目 3（J. Hurwitz）在灵长类（猕猴）免疫缺陷病毒感染疫苗接种模型中实施了项目 1 和 2 的研究结果，并开发了最佳的疫苗生产方案。项目 4（K. Slobod）以这些研究为基础，启动了由免疫原性包膜组合组成的疫苗的安全性和有效性的临床试验。