ADVANCING VACCINE ADJUVANT RESEARCH FOR TUBERCULOSIS (AVAR-T)

第一章 结核分枝杆菌（Mtb），结核病的病原体，仍然是单一传染性病原体导致死亡的主要原因之一，包括艾滋病毒感染者，他们的结核病激活风险增加，结核病治疗效果较差。 （二） 该计划的目标是通过佐剂与结核分枝杆菌免疫原的并行比较，进一步开发预防性（包括接种后）结核疫苗，并建立通过不同机制起作用的佐剂的免疫学特征，促进最有前途的佐剂的鉴定：用于临床开发的结核分枝杆菌免疫原候选物和保护免疫相关物的潜在鉴定。 第三章 将使用小鼠模型对几种佐剂与三种Mtb抗原的组合进行系统评价，以获得佐剂/Mtb抗原制剂的子集，其将用于非人灵长类动物（NHP）模型，以实现IND开发。 四、 对于疫苗攻击研究，研究人员将使用充分表征的Mtb菌株和BCG SSI疫苗作为与最有希望的佐剂：Mtb免疫原候选物的比较。

1) Mycobacterium tuberculosis (Mtb), the causing agent of tuberculosis remains one of the leading cause of death from a single infectious agent, including in people living with HIV who have an increased risk of TB disease activation and poorer TB treatment outcomes. 2) The goal of this program is to further the development of preventive, including postexposure, TB vaccines through side-by-side comparisons of adjuvants in combination with Mtb immunogens, and to establish immunological profiles of adjuvants that work through different mechanisms, facilitating the identification of the most promising adjuvant:Mtb immunogen candidates for clinical development and potential identification of immune correlates of protection. 3) A systematic evaluation of several adjuvants in combination with three Mtb antigens will be conducted using mouse models to obtain a subset of adjuvant/Mtb antigen formulations that will be used in a non-human primate (NHP) model for enabling IND development. 4) For vaccine challenge studies, the investigators will use well-characterized Mtb strains and the BCG SSI vaccine as a comparison against the most promising adjuvant:Mtb immunogen candidate.