CHEMISTRY AND IMMUNOLOGY OF STREPTOCOCCAL M PROTEINS

链球菌 M 蛋白的化学和免疫学

• 批准号: 2671658
• 负责人: JAMES B. DALE
• 金额: $ 21.24万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2671658
• 关键词: Salmonella typhi; Streptococcus pyogenes; Streptococcus vaccine; T lymphocyte; Vibrio cholerae; bacterial antigens; bacterial proteins; bactericidal immunity; drug design /synthesis /production; fusion gene; human tissue; laboratory mouse; laboratory rabbit; molecular cloning; mucosal immunity; opsonin; protein sequence; protein structure; recombinant proteins; serotyping; tissue /cell culture; vaccine development

DESCRIPTION (Adapted from applicant's abstract): The overall goal of this project is to develop a safe and effective vaccine that would prevent group A streptococcal infection. Previous studies have shown that M proteins, the major protective antigens of these organisms, contain both protective as well as potentially harmful tissue- crossreactive epitopes. The previous funding period focused on the identification of protective epitopes of "rheumatogenic" M proteins and their separation from the potentially harmful autoimmune epitopes. The Specific Aims for this renewal proposal are: 1) To determine the primary structures of defined regions of selected serotypes of M proteins that contain protective as opposed to tissue-crossreactive epitopes. 2) To construct recombinant, multivalent M protein vaccines and to determine protein conformations that evoke optimal protective immune responses in laboratory animals. 3) To determine indirectly the potential protective efficacy of multivalent M protein vaccines. 4) To develop strategies of mucosal delivery of multivalent M proteins that evoke local and systemic protective immune response. 5) To determine the minimal primary structures of selected M proteins that are capable of activating bactericidal T lymphocytes in vitro.

描述（改编自申请人的摘要）：总体目标 该项目旨在开发一种安全有效的疫苗 预防A族链球菌感染。 先前的研究表明 M蛋白，这些生物体的主要保护性抗原， 含有保护性组织和潜在有害组织 交叉反应表位。 上一期资助的重点是 鉴定“风湿性”M 蛋白的保护表位和 它们与潜在有害的自身免疫表位分离。 这 该更新提案的具体目标是： 1) 确定 M 蛋白选定血清型的确定区域的一级结构 含有保护性而非组织交叉反应性表位。 2） 构建重组多价 M 蛋白疫苗并 确定激发最佳保护性免疫的蛋白质构象 实验动物的反应。 3）间接确定 多价 M 蛋白疫苗的潜在保护功效。 4） 开发多价 M 蛋白的粘膜递送策略 引起局部和全身的保护性免疫反应。 5）确定 所选 M 蛋白的最小一级结构 体外激活杀菌性T淋巴细胞。