Conservation of meningococcal antigens in the genus Neisseria.
Conservation of meningococcal antigens in the genus Neisseria.
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DOI：
10.1128/mbio.00163-13
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发表时间：
2013-06-11
期刊：
影响因子：
6.4
通讯作者：
Donati C
中科院分区：
文献类型：
--
作者：
Muzzi A;Mora M;Pizza M;Rappuoli R;Donati C
脑膜炎奈瑟氏菌是细菌性脑膜炎和败血症的主要原因之一，是奈瑟氏菌属的成员，该属包括在许多动物的粘膜中定殖的物种。三种脑膜炎球菌蛋白，H因子结合蛋白（fHbp），奈瑟氏球菌肝素结合抗原（NHBA），和N。脑膜炎奈瑟氏球菌粘附素A（NadA）已被描述为针对血清群B脑膜炎奈瑟氏球菌的保护性抗原，并且它们已被用作临床前和临床研究中的疫苗组分。在疫苗制剂中，fHbp和NHBA分别与GNA 2091和GNA 1030蛋白融合，以增强蛋白稳定性和免疫原性。为了确定疫苗接种对奈瑟氏球菌的可能影响，我们确定了奈瑟氏球菌属可用基因组序列中这些抗原的存在、分布和保守性，发现fHbp、NHBA和NadA仅在人类定殖的物种中保守，而GNA 1030和GNA 2091在许多人类和非人类奈瑟氏球菌中保守。序列分析表明，同源重组有助于形成NHBA和fHbp的进化和分布，其中三个主要的变体已被定义。fHbp变体3可能是脑膜炎球菌fHbp的祖先形式，而来自灰奈瑟氏球菌的fHbp变体1通过重组事件被引入脑膜炎奈瑟氏球菌。fHbp变体2是将来自变体1的483 bp的片段插入变体3背景中的重组事件的结果。这些数据表明，在人类上呼吸道定植的奈瑟菌之间存在着高速率的遗传物质交换。健康个体的上呼吸道是一个复杂的生态系统，由许多细菌物种定殖。其中，有奈瑟氏菌属的代表，包括脑膜炎奈瑟氏菌，细菌性脑膜炎和败血症的主要原因。考虑到奈瑟菌和致病菌种之间的密切关系，针对脑膜炎奈瑟菌的蛋白质疫苗有可能影响奈瑟菌的其他奈瑟菌菌种。出于这个原因，我们研究了重组疫苗4CMenB的抗原组分的分布和进化历史，该疫苗最近在欧洲以Bexsero®的商业名称获得批准。我们发现，fHbp，NHBA，和NadA可以在一些人类的哺乳动物物种中发现，这些抗原的进化基本上是由高速率的遗传交换，发生在同一环境中的奈瑟氏球菌菌株之间。
Neisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genus Neisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), and N. meningitidis adhesin A (NadA), have been described as antigens protective against N. meningitidis of serogroup B, and they have been employed as vaccine components in preclinical and clinical studies. In the vaccine formulation, fHbp and NHBA were fused to the GNA2091 and GNA1030 proteins, respectively, to enhance protein stability and immunogenicity. To determine the possible impact of vaccination on commensal neisseriae, we determined the presence, distribution, and conservation of these antigens in the available genome sequences of the genus Neisseria, finding that fHbp, NHBA, and NadA were conserved only in species colonizing humans, while GNA1030 and GNA2091 were conserved in many human and nonhuman neisseriae. Sequence analysis showed that homologous recombination contributed to shape the evolution and distribution of both NHBA and fHbp, three major variants of which have been defined. fHbp variant 3 was probably the ancestral form of meningococcal fHbp, while fHbp variant 1 from N. cinerea was introduced into N. meningitidis by a recombination event. fHbp variant 2 was the result of a recombination event inserting a stretch of 483 bp from variant 1 into the variant 3 background. These data indicate that a high rate of exchange of genetic material between neisseriae that colonize the human upper respiratory tract exists. The upper respiratory tract of healthy individuals is a complex ecosystem colonized by many bacterial species. Among these, there are representatives of the genus Neisseria, including Neisseria meningitidis, a major cause of bacterial meningitis and sepsis. Given the close relationship between commensal and pathogenic species, a protein-based vaccine against N. meningitidis has the potential to impact the other commensal species of Neisseria. For this reason, we have studied the distribution and evolutionary history of the antigen components of a recombinant vaccine, 4CMenB, that recently received approval in Europe under the commercial name of Bexsero®. We found that fHbp, NHBA, and NadA can be found in some of the human commensal species and that the evolution of these antigens has been essentially shaped by the high rate of genetic exchange that occurs between strains of neisseriae that cocolonize the same environment.