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Vaccine Potential of the Neisseria meningitidis 2086 Lipoprotein

机译：脑膜炎奈瑟菌2086脂蛋白的疫苗潜力

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A novel antigen that induces cross-reactive bactericidal antibodies against a number of Neisseria meningitidis strains is described. This antigen, a ～28-kDa lipoprotein called LP2086, was first observed within a complex mixture of soluble outer membrane proteins (sOMPs) following a series of fractionation, protein purification, and proteomics steps. Approximately 95 different neisserial isolates tested positive by Western blotting and PCR screening methods for the presence of the protein and the gene encoding LP2086. The strains tested included isolates of N. meningitidis serogroups A, B, C, W135, and Y, Neisseria gonorrhoeae, and Neisseria lactamica. To better understand the microheterogeneity of this protein, the 2086 genes from 63 neisserial isolates were sequenced. Two different subfamilies of LP2086 were identified based on deduced amino acid sequence homology. A high degree of amino acid sequence similarity exists within each 2086 subfamily. The highest degree of genetic diversity was seen between the two subfamilies which share approximately 60 to 75% homology at the nucleic acid level. Flow cytometry (fluorescence-activated cell sorting) analyses and electron microscopy indicated that the LP2086 is localized on the outer surface of N. meningitidis. Antiserum produced against a single protein variant was capable of eliciting bactericidal activity against strains expressing different serosubtype antigens. Combining one recombinant lipidated 2086 (rLP2086) variant from each subfamily with two rPorA variants elicited bactericidal activity against all strains tested. The rLP2086 family of antigens are candidates worthy of further vaccine development.
机译：描述了一种新型抗原，该抗原诱导针对多种脑膜炎奈瑟氏球菌菌株的交叉反应性杀菌抗体。在一系列分离，蛋白质纯化和蛋白质组学步骤之后，首次在可溶性外膜蛋白（sOMP）的复杂混合物中观察到了这种称为LP2086的〜28 kDa脂蛋白抗原。通过蛋白质印迹和PCR筛选方法，大约有95种不同的奈瑟氏菌分离株检测出该蛋白质和编码LP2086的基因为阳性。测试的菌株包括 N的分离株。脑膜炎血清群A，B，C，W135和Y，淋病奈瑟氏球菌和乳酸奈瑟氏菌。为了更好地了解这种蛋白质的微异质性，对来自63个奈瑟菌分离株的2086个基因进行了测序。基于推导的氨基酸序列同源性鉴定了LP2086的两个不同的亚家族。每个2086个亚家族中都存在高度的氨基酸序列相似性。在两个亚科之间观察到最高程度的遗传多样性，这两个亚科在核酸水平上具有大约60％至75％的同源性。流式细胞仪（荧光激活细胞分选）分析和电子显微镜表明，LP2086定位于 N的外表面。脑膜炎。针对单一蛋白质变体产生的抗血清能够引发针对表达不同血清亚型抗原的菌株的杀菌活性。将来自每个亚科的一种重组脂化的2086（rLP2086）变体与两个rPorA变体组合，可引发针对所有测试菌株的杀菌活性。 rLP2086抗原家族是值得进一步疫苗开发的候选药物。

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