CHEMISTRY AND IMMUNOLOGY OF STREPTOCOCCAL M PROTEINS

描述（改编自申请人摘要）：总体目标 该项目旨在开发一种安全有效的疫苗， 预防A群链球菌感染。 先前的研究表明 M蛋白，这些生物体的主要保护性抗原， 既有保护性组织也有潜在的有害组织 交叉反应表位 上一个供资期的重点是 “致风湿性”M蛋白的保护性表位的鉴定， 它们与潜在有害的自身免疫表位的分离。 的 本更新建议的具体目标是：1）确定 选定M蛋白血清型的确定区域的一级结构 含有保护性而不是组织交叉反应性表位。 （二） 构建重组多价M蛋白疫苗， 确定引起最佳保护性免疫的蛋白质构象 实验室动物的反应。 3)间接确定 多价M蛋白疫苗的潜在保护效力。 四、 为了开发粘膜递送多价M蛋白的策略， 引起局部和全身保护性免疫应答。 5)以确定 所选M蛋白的最小一级结构能够 在体外激活杀菌性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.