Vaccine potential of the Neisseria meningitidis 2086 lipoprotein
Vaccine potential of the Neisseria meningitidis 2086 lipoprotein
复制标题
DOI：
10.1128/iai.72.4.2088-2100.2004
复制
发表时间：
2004-04-01
影响因子：
3.1
通讯作者：
Zlotnick, GW
中科院分区：
文献类型：
--
作者：
Fletcher, LD;Bernfield, L;Zlotnick, GW
描述了一种新的抗原，其诱导针对许多脑膜炎奈瑟氏菌菌株的交叉反应性杀菌抗体。这种抗原类似于28-kDa脂蛋白，称为LP 2086，在经过一系列分级分离、蛋白纯化和蛋白质组学步骤后，首先在可溶性外膜蛋白（sOMP）的复杂混合物中观察到。通过蛋白质印迹和PCR筛选方法检测约95种不同的奈瑟球菌分离株中是否存在蛋白质和编码LP 2086的基因，结果为阳性。供试菌株包括N.脑膜炎血清群A、B、C、W135和Y，淋病奈瑟菌和内酰胺奈瑟菌。为了更好地了解这种蛋白质的微观异质性，从63个奈瑟球菌分离株的2086个基因进行测序。基于推导的氨基酸序列同源性鉴定了LP 2086的两个不同亚家族。在每个2086亚家族内存在高度的氨基酸序列相似性。遗传多样性程度最高的两个亚家族之间的共享约60至75%的同源性在核酸水平。流式细胞仪（荧光激活细胞分选）分析和电子显微镜表明，LP 2086定位于N.脑膜炎针对单一蛋白变体产生的抗血清能够引起针对表达不同血清亚型抗原的菌株的杀菌活性。将来自每个亚家族的一个重组脂化2086（rLP 2086）变体与两个rPorA变体组合引起对所有测试菌株的杀菌活性。rLP 2086抗原家族是值得进一步疫苗开发的候选者。
A novel antigen that induces cross-reactive bactericidal antibodies against a number of Neisseria meningitidis strains is described. This antigen, a similar to28-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.