BACTERIAL POLYSACCHARIDE CROSS-REACTIVE WITH MENINGOCOCCAL GROUP A POLYSACCHARIDE

细菌多糖与脑膜炎球菌 A 群多糖发生交叉反应

• 批准号: 3965845
• 负责人: R SCHNEERSON
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3965845
• 关键词: Escherichia coli; Neisseria meningitidis; Neisseria meningitidis vaccine; active immunization; antibacterial antibody; bacterial antigens; bacterial capsules; bacterial meningitis; bacterial polysaccharides; bactericidal immunity; communicable diseases; cross immunity; epidemiology; human therapy evaluation; immunoconjugates; immunodiffusion; immunological substance; immunoprecipitation; microorganism immunology; monoclonal antibody; passive immunization; serotyping; virulence

Similar to other encapsulated bacterial pathogens, anti-capsular polysaccharide antibodies confer immunity to diseases caused by Neisseria meningitidis. Group A meningococcal diseases have a different epidemiology than the other pathogenic serogroups. In Africa, Group A meningitis is endemic with high frequency; in other parts of the world, Group A causes epidemics. In both situations, asymptomatic carriage of Group A meningococci is low. In the U.S., disease or carriage of Group A meningococci can be considered as absent for the past 30 years. Yet, most children and young adults throughout the world have Group A polysaccharide antibodies. During investigations to find cross-reactive polysaccharides among non-pathogenic normal flora that might account for this ubiquitous "natural" immunity, two Escherichia coli capsular polysaccharides, K93 and K51, were discovered and their serological properties and structures characterized. Despite their antigenic cross-reactivity, the K93 and K51 failed to absorb Group A antibodies from pre and post immunization sera of vaccinates injected with Group A meningococcal vaccine. Importance of the 0-acetyl in the K93 polysaccharide in this cross-reactivity was established. Schemes for synthesis of K93, K51 and Group A polysaccharides with medically useful carrier proteins have been devised in order to prepare conjugates for clinical evaluation. Such products should be more effective immunogens against Group A meningitis in infants and children than Group A vaccine. A patient, without malignancy and with high levels of a monoclonal antibody reactive with both Group B meningococcal and E. coli K1 capsular polysaccharides, was discovered. The specificity and protective effects of this monoclonal antibody were characterized. Its therapeutic effect in the treatment of Group B meningococcal meningitis is planned to be studied.

类似于其他荚膜细菌病原体，具有抗荚膜性