NOVEL GROUP A STREPTOCOCCUS HUMAN VACCINE CANDIDATES

新型 A 组链球菌人类疫苗候选者

• 批准号: 6804318
• 负责人: James MALLORY Musser
• 金额: $ 64.48万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6804318
• 关键词: Macaca fascicularis; Streptococcus pyogenes; Streptococcus vaccine; active immunization; bacterial antigens; bacterial proteins; biotherapeutic agent; clinical research; cooperative study; disease /disorder model; drug discovery /isolation; echocardiography; flow cytometry; genetic strain; hairless mouse; host organism interaction; human subject; nonhuman therapy evaluation; pharyngitis; protein purification; protein quantitation /detection; recombinant proteins; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): This study is designed to identify one or more conserved group A Streptococcus (GAS) proteins suitable for use as a safe and efficacious human vaccine worldwide. The key goal of the proposed research is to use genome-wide methods of contemporary vaccinology to identify one or more conserved GAS proteins that will significantly protect monkeys from pharyngitis caused by challenge with a strain expressing a heterologous M protein serotype. A conservative estimated timeline is that by the end of the 5-year research period, the antigen(s) will be ready for detailed toxicity testing prior to beginning phase I human trials. The international investigative team composed of academic and pharmaceutical industry collaborators proposes the following line of research involving a "reverse vaccinology" strategy: Aim 1: Use two mouse models of invasive GAS disease to confirm extensive preliminary data that novel candidate GAS antigens significantly protect immunized mice challenged with a GAS strain expressing a heterologous M protein serotype. Aim 2: Determine if the proteins satisfying the mouse screen criteria described in aim (1) above are conserved in natural populations of GAS, expressed on the cell surface of genetically diverse GAS strains, and expressed in vivo during diverse types of human infections (pharyngitis, invasive infections, etc). Aim 3: Use a recently-described monkey model that mimics human pharyngitis to determine if one or more of the candidate vaccine antigens we identify in aim (1) and (2) significantly protects against pharyngitis caused by a GAS strain expressing a heterologous M protein serotype.

描述（由申请人提供）： 这项研究旨在鉴定一个或多个保守的A链球菌（气体）蛋白，适合于全球安全有效的人类疫苗。拟议的研究的关键目的是使用全基因组的当代疫苗学方法来识别一种或多种保守的气体蛋白，这些蛋白质将显着保护猴子免受咽炎的影响，这是由表达异源M蛋白血清型的挑战引起的咽炎。保守的估计时间表是，到5年研究期结束时，抗原将在开始I期人类试验之前准备进行详细的毒性测试。由学术和制药行业合作者组成的国际调查团队提出了以下研究领域，涉及“反疫苗学”策略： AIM 1：使用两种侵入性气体疾病的小鼠模型来确认新型候选气体抗原的广泛初步数据可显着保护对表达异源M蛋白质型气体菌株挑战的免疫小鼠。 AIM 2：确定满足上述目标（1）中描述的小鼠筛查标准的蛋白质是否在自然气体中保守，在遗传多样的气体菌株的细胞表面表达，并在各种人类感染类型（咽炎，侵入性感染等）中以体内表达。 AIM 3：使用最近描述的猴子模型，该模型模仿人咽炎，以确定我们在AIM（1）和（2）中鉴定出的一种或多种候选疫苗抗原是否可以显着保护由表达异源M蛋白质蛋白质型的气体菌株引起的咽炎。