TUBERCULOSIS VACCINE DEVELOPMENT

结核病疫苗的开发

• 批准号: 9161858
• 负责人: CHRISTOPHER CASE
• 金额: $ 200万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-26 至 2020-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9161858
• 关键词: Adenoviruses; Adult; Aerosols; Animal Model; Antigens; Attenuated; Cause of Death; Cessation of life; Clinical; Data; HIV; Immune response; Immunity; Immunization; Infection; Influenza; Intravenous; Lung; Macaca; Macaca mulatta; Modality; Modeling; Mucous Membrane; Mycobacterium tuberculosis; Pathogenesis; Population; Proteins; Route; SIV; Scheme; Site; T cell response; T-Lymphocyte; Testing; Tuberculosis; Tuberculosis Vaccines; Vaccines; arm; base; experience; nonhuman primate; prevent; research study; vaccination against tuberculosis; vaccine development

One third of the world's population is infected with Mycobacterium tuberculosis (TB). Annually, more than 9 million become sick, and there are more than 1.5 million TB related deaths. It is one of the leading causes of death in HIV-infected adults. In particular, TB resides and replicates in the lung. Even in BCG vaccinated adults, it normally takes 2 to 3 weeks for T cells, the primary arm of immunity against TB, to respond in the lung. The VRC has developed vaccine strategies to attenuate or possibly prevent pathogenesis following infection with TB by eliciting potent T cell responses at the site of infection, the lung mucosa. Aerosol delivery of antigens has proven to be a potent immunization scheme in the lung; the VRC has extensive experience with such delivery in the nonhuman primate model and has shown strong immune responses protective against influenza and SIV pathogenesis by such a modality. In addition, VRC data show that very strong T cell responses are elicited that remain relatively stable in the lung for a year or more in nonhuman primates. Based on these data, the VRC will evaluate the hypothesis that aerosol delivery of TB antigens to the lung will provide more rapid and potent T-cell responses compared to standard BCG vaccination, resulting in decreased pathogenesis and/or attenuated infection by TB. To test this hypothesis, detailed research studies in a suitable animal model will be performed. The choice of species, TB challenge strain, challenge delivery route, and other variables will be studied.

世界上三分之一的人口感染了结核分枝杆菌 (TB)。每年有超过 900 万人患病，超过 150 万人与结核病相关死亡。它是艾滋病毒感染者成人死亡的主要原因之一。特别是，结核病在肺部驻留和复制。即使在接种卡介苗的成年人中，T 细胞（抵抗结核病的主要免疫力）通常也需要 2 至 3 周的时间才能在肺部产生反应。 VRC 已开发出疫苗策略，通过在感染部位（肺粘膜）引发有效的 T 细胞反应，来减轻或可能预防结核病感染后的发病机制。抗原气雾输送已被证明是一种有效的肺部免疫方案； VRC 在非人类灵长类动物模型中进行此类递送方面拥有丰富的经验，并通过这种方式表现出强大的免疫反应，可预防流感和 SIV 发病机制。此外，VRC 数据显示，在非人类灵长类动物中，引发了非常强烈的 T 细胞反应，这种反应在肺部保持相对稳定一年或更长时间。 根据这些数据，VRC 将评估以下假设：与标准 BCG 疫苗接种相比，将结核抗原气雾输送至肺部将提供更快速、更有效的 T 细胞反应，从而减少结核病的发病机制和/或减弱结核病感染。 为了检验这一假设，将在合适的动物模型中进行详细的研究。 将研究物种、结核病攻击菌株、攻击传递途径和其他变量的选择。