State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, PR China.
Hubei Provincial Center for Disease Control and Prevention, Wuhan, PR China.
Vaccine. 2018 Apr 5;36(15):1983-1989. doi: 10.1016/j.vaccine.2018.02.112. Epub 2018 Mar 7.
To systematically investigate the prevalence and genetic characteristics of 4CMenB and rLP2086 vaccine candidates among Neisseria meningitidis serogroup B (NmB) in China.
A total of 485 NmB strains isolated in 29 provinces of China between 1968 and 2016 were selected from the culture collection of the national reference laboratory according to the isolation year, location, and source. Multi-locus sequence typing (MLST) and porA gene sequencing were performed on all 485 study strains; PCR was used to detect the fHbp, nadA, and nhba gene of 432 strains; positive amplification products from the fHbp and nadA genes from all strains, as well as those of the nhba gene from 172 representative strains, were sequenced.
MLST results showed that the predominant (putative) clonal complexes (CCs) of NmB isolates have changed over time in China. While strains that could not be assigned to existing (p)CCs were the biggest proportion, CC4821 was the most prevalent lineage (36.0%) since 2005. PCR and sequence analysis revealed that the 4CMenB and rLP2086 vaccine candidates were highly diverse. Respectively, 152 PorA genotypes and 83 VR2 sequences were identified with significant diversity within a single CC; the complete nadA gene was found in ten of 432 study strains; fHbp was present in most strains (422/432) with variant 2 predominating (82.9%) in both patient- and carrier- derived isolates; almost all strains harbored the nhba gene while sequences were diverse.
With regards to clonal lineages and vaccine candidate proteins, NmB isolates from China were generally diverse. Further studies should be performed to evaluate the cross-protection of present vaccines against Chinese NmB strains.
系统研究中国脑膜炎奈瑟菌 B 群（NmB）中 4CMenB 和 rLP2086 候选疫苗的流行率和遗传特征。
根据分离年份、地点和来源，从国家参考实验室的培养物库中选择了 1968 年至 2016 年期间在中国 29 个省分离的 485 株 NmB 菌株。对所有 485 株研究菌株进行多位点序列分型（MLST）和 porA 基因测序；对 432 株菌株进行 fHbp、nadA 和 nhba 基因的 PCR 检测；对所有菌株的 fHbp 和 nadA 基因的阳性扩增产物以及 172 株代表性菌株的 nhba 基因进行测序。
MLST 结果表明，中国 NmB 分离株的主要（假定）克隆复合体（CC）随时间发生了变化。虽然无法归入现有（p）CC 的菌株比例最大，但自 2005 年以来，CC4821 是最流行的谱系（36.0%）。PCR 和序列分析显示，4CMenB 和 rLP2086 候选疫苗高度多样化。分别在单个 CC 内鉴定出 152 种 PorA 基因型和 83 种 VR2 序列，具有显著的多样性；在 432 株研究菌株中发现了 10 株完整的 nadA 基因；fHbp 存在于大多数菌株（422/432）中，患者和携带者来源的分离株中主要存在变体 2（82.9%）；几乎所有菌株都携带 nhba 基因，序列多样。
就克隆谱系和疫苗候选蛋白而言，中国的 NmB 分离株通常具有多样性。应进一步开展研究，评估现有疫苗对中国 NmB 菌株的交叉保护作用。
