ADVANCING VACCINE ADJUVANT RESEARCH FOR TUBERCULOSIS (AVAR-T)

推进结核病疫苗佐剂研究 (AVAR-T)

• 批准号: 10703854
• 负责人: WARWICK BRITTON
• 金额: $ 245.36万
• 依托单位: UNIVERSITY OF SYDNEY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703854
• 关键词: Adjuvant; Aerosols; Animals; Antigens; Cause of Death; Cells; Development; Disease; Dose; Evaluation; Formulation; Goals; HIV; Human; Immune; Immunity; Immunologics; In Vitro; Inbred Mouse; Infectious Agent; Macaca mulatta; Modeling; Mus; Mycobacterium tuberculosis; Mycobacterium tuberculosis antigens; Persons; Preventive; Research; Research Personnel; Risk; Side; Treatment outcome; Tuberculosis; Tuberculosis Vaccines; Vaccine Adjuvant; Vaccines; Work; clinical candidate; clinical development; mouse model; nonhuman primate; novel; programs; tuberculosis treatment

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.

1) 结核病致病菌结核分枝杆菌 (Mtb) 仍然是单一传染源导致死亡的主要原因之一，包括结核病激活风险增加和结核病治疗结果较差的艾滋病毒感染者。 2) 该计划的目标是通过佐剂与结核分枝杆菌免疫原的并排比较，进一步开发预防性结核病疫苗，包括暴露后结核病疫苗，并建立通过不同机制起作用的佐剂的免疫学特征，促进鉴定最有前途的佐剂：用于临床开发的 Mtb 免疫原候选物和保护性免疫相关性的潜在鉴定。 3) 将使用小鼠模型对几种佐剂与三种 Mtb 抗原组合进行系统评估，以获得佐剂/Mtb 抗原制剂的子集，该制剂将用于非人灵长类动物 (NHP) 模型，以实现 IND 开发。 4) 对于疫苗攻击研究，研究人员将使用特征明确的 Mtb 菌株和 BCG SSI 疫苗与最有希望的佐剂：Mtb 免疫原候选物进行比较。