Objective: To investigate the molecular characteristics of serogroup B neisseria meningitidis in China. Methods: Total of 485 (100 strains isolated from cerebrospinal fluid or blood samples of encephalomyelitis cases, and 385 strains isolated from nasopharynx of healthy carriers) Meningococcal serogroup B (MenB) strains, isolated from 29 provinces of China between 1968 and 2016, were analyzed by multilocus sequence typing (MLST) and PorA typing methods. Further, the genetic diversity of three MenB vaccine proteins, FHbp, NadA and NHBA, were analyzed. Results: The 485 study strains belonged to 270 sequence types (STs), 107 of which (representing 211 strains) could be grouped into ten clonal complexes (CC). CC4821 has been the predominant lineage in China since 2005 (28.7%, n=139). The most common PorA types of MenB strains from invasive meningococcal cases were P1.5-2,2-2 (10.0%, n=10), P1.5-1,2-2 (9.0%, n=9) and P1.5-1,10-4 (9.0%, n=9). Four hundred and twenty one strains had intact fhbp gene; variant 1, 2 and 3 accounted for 12.8% (54 strains), 85.0% (358 strains) and 2.2% (9 strains) respevtively. Ten out of 432 strains (2.3%) contained complete nadA gene. All the 172 strains for which the nhba gene was sequenced had intact gene sequence which corresponded to 68 peptide types. Conclusion: CC4821 was the predominant CC of MenB strains in China; the vaccine proteins were diverse about the sequences. The vaccine proteins should be carefully selected when developing MenB vaccines in China.
目的： 分析中国B群脑膜炎奈瑟菌分子流行病学特征。 方法： 485株B群脑膜炎奈瑟菌为1968—2016年分离和收集于29个省份的菌株，包括流行性脑脊髓膜炎（流脑）病例脑脊液或血液标本分离菌株100株，健康带菌者鼻咽部分离菌株385株。根据多位点序列分型（MLST）网站公布的方法，对菌株进行PorA外膜蛋白分型和MLST分型，采用Bionumerics软件分析序列型（ST型），构建最小生成树；针对B群脑膜炎奈瑟菌蛋白疫苗的主要成分FHbp、NadA和NHBA蛋白进行分子型别分布和序列特征分析。 结果： 485株B群脑膜炎奈瑟菌分为270种ST型，其中107种ST型（211株菌）可归入已知的10个克隆群，163种ST型（274株）不能归入任何克隆群；CC4821为主要流行的克隆群（28.7%，139株）。病例分离菌株的主要PorA型为P1.5-2，2-2（10.0%，10株）、P1.5-1，2-2（9.0%，9株）和P1.5-1，10-4（9.0%，株）。421株含有完整的FHbp氨基酸序列，其中变异1型（v1）、2型（v2）和3型（v3）(菌株分别占12.8%（54株）、85.0%（358株）和2.2%（9株）。432株完成)nadA(基)因测序，其中10株(（2.3%）含有完整的)nadA(基)因。172株完成nhba基因测序，均具有完整的nhba基因序列，其中170株的NHBA氨基酸序列共分为68个型，呈现出多态性特征。 结论： 中国B群脑膜炎奈瑟菌优势克隆群为CC4821；其疫苗相关蛋白多态性较强。中国应该根据本国菌株的特征慎重选择B群流脑疫苗候选蛋白。.
Keywords: Molecular characteristic; Neisseria meningitidis, Serogroup B; Vaccine antigen.