CHEMISTRY AND IMMUNOLOGY OF STREPTOCOCCAL M PROTEINS

描述(改编自申请者摘要)：总体目标 该项目旨在开发一种安全有效的疫苗， 预防A组链球菌感染。先前的研究表明 M蛋白，这些生物的主要保护性抗原， 既含有保护性的，也含有潜在的有害组织- 交叉反应表位。上一个资助期的重点是 “风湿致病”M蛋白保护性表位的鉴定 它们与潜在有害的自身免疫表位分离。这个 本次续签提案的具体目标是：1)确定 部分血清型M蛋白特定区域的一级结构 包含保护性表位，而不是组织交叉反应表位。2) 构建重组多价M蛋白疫苗，并 确定能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效果。4) 发展多价M蛋白的粘膜递送策略 引起局部和系统的保护性免疫反应。5)确定 选定的M种蛋白质的最小一级结构 在体外激活杀菌T淋巴细胞。

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.