Improved meningococcal vesicle vaccines

改进的脑膜炎球菌囊泡疫苗

• 批准号: 6772650
• 负责人: David Manh-Tung Vu
• 金额: $ 5.05万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772650
• 关键词: Neisseria meningitidis vaccine; SDS polyacrylamide gel electrophoresis; antibody; bacterial antigens; bacterial proteins; drug design /synthesis /production; enzyme linked immunosorbent assay; immunization; infant animal; laboratory mouse; laboratory rat; membrane; polymerase chain reaction; postdoctoral investigator; vaccine development; vesicle /vacuole

DESCRIPTION (provided by applicant): Currently there are no vaccines available for the prevention of disease caused by group B N. meningitidis strains, which accounts for 30-80% of meningococcal disease. Outer membrane vesicle vaccines are known to confer protection in humans but the bactericidal activity is strain-specific. My mentors (Moe et al.) recently showed that sequential immunization with outer membrane vesicle vaccines prepared from three heterologous meningococcal strains, each with different capsular groups, PorA serosubtypes, and PorB serotypes, elicits broadly protective bactericidal antibodies against genetically diverse meningococcal strains, in part by eliciting antibodies to conserved proteins that typically are poorly immunogenic. I propose to develop improved vesicle vaccines by: (1) over-expressing certain highly conserved antigens, such as Neisserial surface protein A (NspA), that have been shown to elicit protective antibodies during sequential immunization, and (2) eliminating antigens that elicit antibodies that do not confer protection, or variable antigens that elicit strain-specific antibodies.

描述（由申请方提供）：目前尚无预防B N群引起疾病的疫苗。脑膜炎菌株，占脑膜炎球菌病的30-80%。已知外膜囊泡疫苗在人类中提供保护，但杀菌活性是菌株特异性的。我的导师（莫伊等人）最近表明，用由三种异源脑膜炎球菌菌株制备的外膜囊泡疫苗进行顺序免疫，每种菌株具有不同的荚膜群、PorA血清亚型和PorB血清型，部分通过引发针对通常免疫原性差的保守蛋白的抗体，引发针对遗传多样性脑膜炎球菌菌株的广泛保护性杀菌抗体。我建议通过以下方式开发改进的囊泡疫苗：（1）过表达某些高度保守的抗原，如奈瑟球菌表面蛋白A（NspA），这些抗原已被证明在序贯免疫过程中引发保护性抗体，以及（2）消除引发不提供保护的抗体的抗原，或引发菌株特异性抗体的可变抗原。