Improved meningococcal vesicle vaccines

说明(申请人提供)：目前还没有疫苗可用于预防由占脑膜炎双球菌疾病30%-80%的B群脑膜炎奈瑟菌引起的疾病。已知外膜囊泡疫苗对人类具有保护作用，但其杀菌活性是菌株特有的。我的导师(Moe等人)最近的研究表明，由三个不同的脑膜炎球菌株制备的外膜泡囊疫苗顺序免疫，每个株具有不同的衣膜组、PorA血清亚型和PorB血清型，诱导针对遗传多样性的脑膜炎球菌株的广泛保护性杀菌抗体，部分是通过诱导针对通常免疫原性较差的保守蛋白的抗体。我建议通过以下方式开发改进的水泡疫苗：(1)过度表达某些高度保守的抗原，如NeisSeries表面蛋白A(NSPA)，这些抗原已被证明在顺序免疫中可诱导保护性抗体，以及(2)消除引起不提供保护的抗体的抗原，或引起菌株特异性抗体的可变抗原。

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.