Chemistry and Immunology of Streptococcal M Proteins

链球菌 M 蛋白的化学和免疫学

• 批准号: 7625116
• 负责人: JAMES B. DALE
• 金额: $ 34.92万
• 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 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7625116
• 关键词: Adjuvant; Amino Acids; Antibodies; Antibody Formation; Antigens; Autoimmune Process; Biological Assay; Chemistry; Child; Clinical; Complex; Data; Drops; Drug Formulations; Epitopes; Escherichia coli; Genes; Geographic Locations; Goals; Immune; Immune Sera; Immune response; Immunization; Immunoglobulin Fragments; Immunology; Individual; Infection; Intramuscular; Intramuscular Injections; Laboratory Animals; Length; Link; Lipid A; Liposomes; Measures; Membrane Proteins; Molecular Conformation; Mus; N-terminal; North America; Nose; Oryctolagus cuniculus; Peptide Fragments; Peptides; Pharyngitis; Positioning Attribute; Protein Fragment; Proteins; Recombinants; Route; Saliva; Salivary; Schools; Series; Serotyping; Serum; Specific qualifier value; Streptococcal Infections; Streptococcal Vaccines; Streptococcus pyogenes; Structure; Surface; Testing; Tissues; Vaccines; Virulent; Western Europe; bactericide; base; calcium phosphate; epidemiologic data; hybrid gene; hybrid protein; immunogenic; immunogenicity; intraperitoneal; multiple myeloma M Protein; nanoparticle; periplasm; prevent; protective efficacy; protein aminoacid sequence; research study; retinal S antigen peptide M; streptococcal M protein

The overall goal of this project is to develop a safe and broadly effective vaccine that will prevent group A streptococcal infections. Previous studies have shown that the surface M proteins, which are the major protective antigens, contain tissue-crossreactive epitopes as well as protective epitopes. The serotype-specific protective epitopes may be separated from potentially harmful autoimmune epitopes by using limited N-terminal peptides of M proteins. The protective M protein fragments representing multiple serotypes of group A streptococci may then be combined to form a multivalent vaccine. The specific aims of this proposal are: 1) To identify the primary structures of M proteins or other surface proteins that contain opsonic (protective) epitopes from serotypes of group A streptococci that areepidemiologically important and, therefore, necessary vaccine components, 2) To construct recombinant, multivalent vaccines that evoke optimal opsonic antibody responses in laboratory animals against 26 different serotypes of group A streptococci, 3) To test immune rabbit sera evoked by multivalent vaccines for opsonic and bactericidal antibodies against clinical isolates of group A streptococci collected from children with pharyngitis in 10 geographic sites in the U.S., 4) To develop strategies of intranasal delivery of multivalentM protein-based vaccines that result in secretory and systemic immune responses, and 5) To directly compare the protective immunogenicity of multivalent M protein-based vaccines delivered to mice via either the intramuscular or intranasal routes. In our preliminary studies, we have identified six epidemiologically important serotypes of group A streptococci that are not opsonized by antisera against the N-terminalM protein peptides. We propose a series of experiments to determine the covalent structures of the M proteins, M-like proteins, or other surface proteins that contain opsonic epitopes so that these M serotypes may be included in multivalent vaccines. We will construct a 26-valent vaccine composed of 4 different recombinant, hybrid proteins. The individual hybrid proteins will be tested for protective and tissue-crossreactive immunogenicity after intramuscular injection of rabbits. Because mucosal delivery of streptococcal vaccines may have both immunological and practical advantages over parenteral delivery, we will assess different strategies of intranasal delivery and then directly compare the protective efficacy of i.n. vs i.m. vaccines in mice. The studies should provide the detailed information needed to develop a safe and effective multivalent vaccine that could prevent the majority of streptococcal infections in North America and Western Europe.

该项目的总体目标是研制一种安全有效的疫苗，以预防a群链球菌感染