Improved meningococcal vesicle vaccines

描述（由申请人提供）：目前没有疫苗可用于预防由脑膜炎B群N.菌株引起的疾病，该菌株占脑膜炎球菌病的30-80%。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异性的。我的导师（Moe等人）最近表明，用三种异源脑膜炎球菌菌株制备的外膜囊泡疫苗（每种菌株具有不同的荚膜群、PorA血清亚型和PorB血清型）进行序次免疫，可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，部分原因是通过激发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囊泡疫苗：(1)过度表达某些高度保守的抗原，如Neisserial表面蛋白A (NspA)，这些抗原已被证明在顺序免疫过程中会引发保护性抗体；(2)消除那些引发不具有保护作用的抗体的抗原，或引发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.