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）： 本研究旨在鉴定一种或多种保守的A组链球菌（GAS）蛋白，适合用作全球安全有效的人用疫苗。拟议研究的关键目标是使用当代疫苗学的全基因组方法来鉴定一种或多种保守的GAS蛋白，这些蛋白将显着保护猴子免受表达异源M蛋白血清型的菌株引起的咽炎。保守估计的时间轴是，在5年研究期结束时，抗原将在开始I期人体试验之前准备好进行详细的毒性试验。由学术界和制药业合作者组成的国际调查小组提出了以下涉及“反向疫苗学”策略的研究路线： 目标1：使用侵袭性GAS疾病的两个小鼠模型来证实广泛的初步数据，即新的候选GAS抗原显著保护用表达异源M蛋白血清型的GAS菌株攻击的免疫小鼠。 目标二：确定满足上述目的（1）中描述的小鼠筛选标准的蛋白质是否在天然GAS群体中保守，在遗传多样性GAS菌株的细胞表面上表达，以及在不同类型的人类感染（咽炎、侵入性感染等）期间体内表达。 目标三：使用最近描述的模拟人咽炎的猴模型来确定我们在目的（1）和（2）中鉴定的一种或多种候选疫苗抗原是否显著保护免于由表达异源M蛋白血清型的GAS菌株引起的咽炎。