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首页> 外文OA文献 >Functional Activity of Anti-Neisserial Surface Protein A Monoclonal Antibodies against Strains of Neisseria meningitidis Serogroup B
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Functional Activity of Anti-Neisserial Surface Protein A Monoclonal Antibodies against Strains of Neisseria meningitidis Serogroup B

机译：抗脑膜炎奈瑟氏球菌血清群B株抗奈瑟氏表面蛋白A单克隆抗体的功能活性

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Neisserial surface protein A (NspA) is currently being investigated with humans as a candidate vaccine for the prevention of meningococcal disease. Although NspA is highly conserved, the ability of anti-NspA antibodies to bind to or elicit complement-mediated bactericidal activity against diverse Neisseria meningitidis serogroup B strains is controversial. To evaluate strain differences in NspA surface accessibility and susceptibility to bactericidal activity, we prepared murine immunoglobulin G2a anti-NspA monoclonal antibodies (MAbs) and evaluated their functional activity against 10 genetically diverse N. meningitidis serogroup B strains. By colony Western blot, all 10 strains expressed NspA as detected by one or more MAbs. By flow cytometry, two MAbs were found to bind to the bacterial surface of 6 of the 10 strains. In addition, two strains showed variable NspA surface accessibility for the MAbs despite being uniformly positive for NspA expression by colony Western blotting. Only 4 of the 10 strains were susceptible to anti-NspA complement-mediated bacteriolysis. Passively administered MAb protected infant rats from developing bacteremia after challenge with N. meningitidis serogroup B strain 8047 (surface binding positive, susceptible to anti-NspA bacteriolysis), was poorly protective against strain BZ232 (surface binding variable, resistant to bacteriolysis), and did not protect against strain M986 (surface binding negative, resistant to bacteriolysis). Finally, NspA does not appear to be critical for causing bacteremia, as an NspA knockout from strain 8047 was highly virulent in infant rats. Taken together, these findings suggest that an NspA-based vaccine will need to incorporate additional antigens to elicit broad protection against N. meningitidis serogroup B.
机译：目前正在与人一起研究奈瑟球表面蛋白A（NspA）作为预防脑膜炎球菌疾病的候选疫苗。尽管NspA是高度保守的，但抗NspA抗体结合或引发补体介导的针对多种脑膜炎奈瑟氏球菌血清B株的杀菌活性的能力仍存在争议。为了评估菌株在NspA表面可及性和对杀菌活性的敏感性方面的差异，我们制备了鼠免疫球蛋白G2a抗NspA单克隆抗体（MAbs），并评估了它们对10种遗传多样的脑膜炎双球菌血清B菌株的功能活性。通过菌落Western印迹，通过一种或多种MAb检测，所有10个菌株均表达NspA。通过流式细胞术，发现两个MAb结合至10个菌株中的6个的细菌表面。另外，尽管通过菌落Western印迹对NspA表达一致阳性，但两种菌株对MAb显示出可变的NspA表面可及性。 10个菌株中只有4个对抗NspA补体介导的溶菌作用敏感。被动施用的单克隆抗体可保护婴儿免受脑膜炎双球菌B血清群8047菌株（表面结合阳性，易受NspA溶菌作用）攻击后发展成菌血症，对菌株BZ232的保护性差（表面结合变量，耐细菌分解作用），并且确实做到了不能抵抗M986菌株（表面结合阴性，抗细菌分解作用）。最后，NspA似乎对引起菌血症不是至关重要的，因为8047株的NspA敲除对婴儿大鼠具有高毒性。综上所述，这些发现表明，基于NspA的疫苗将需要掺入其他抗原以引发针对脑膜炎双球菌血清B的广泛保护。

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