波兰 B 群脑膜炎奈瑟菌（2010-2016 年）遗传变异情况，包括 4CMenB 疫苗成分基因。
Genetic variability of Polish serogroup B meningococci (2010-2016) including the 4CMenB vaccine component genes.
机构信息
National Reference Centre for Bacterial Meningitis, National Medicines Institute, Warsaw, Poland.
Institute Pasteur, Invasive Bacterial Infections Unit, Paris, France.
出版信息
Vaccine. 2020 Feb 18;38(8):1943-1952. doi: 10.1016/j.vaccine.2020.01.021. Epub 2020 Jan 21.
Neisseria meningitidis serogroup B (MenB) has recently become the major cause of invasive meningococcal disease in Poland. Therefore, the purpose of this study was to characterize MenB isolates, responsible for invasive meningococcal disease in 2010-2016, by MLST and sequencing of genes encoding proteins used as 4CMenB vaccine antigens. Two methods of coverage estimation were performed: extrapolation of MATS results of Polish meningococci 2010-2011 (exMATS) and gMATS, which combines genotyping and MATS results. Among 662 isolates 20 clonal complexes (CC) were detected, of which the most frequent were CC32, CC41/44 and CC18, accounting for 31.9%, 16.5% and 12.7%, respectively. A total of 111 combinations of PorA variable regions (VR1/VR2) were found, with P1.7,16 (15.0%) and P1.22,14 (13.6%) being prevalent. Vaccine variant VR2:4 was detected in 7.3% of isolates, mainly representing CC41/44 and non-assigned CC. Eighty five fHbp alleles encoding 74 peptide subvariants were revealed. Subvariant 1.1, a component of 4CMenB, was prevalent (24.2%) and found generally in CC32. Typing of the nhba gene revealed 102 alleles encoding 87 peptides. The most frequent was peptide 3 (22.4%), whereas vaccine peptide 2 was detected in 9.8%, mostly among CC41/44. The nadA gene was detected in 34.0% of isolates and the most prevalent was peptide 1 (variant NadA-1; 71.6%), found almost exclusively in CC32 meningococci. Vaccine peptide 8 (variant NadA-2/3) was identified once. Consequently, 292 completed BAST profiles were revealed. Regarding vaccine coverage, 39.7% of isolates had at least one 4CMenB vaccine variant, but according to exMATS and gMATS the coverage was 83.3% and 86.6%, respectively. In conclusion, Polish MenB (2010-2016) was highly diverse according to MLST and gene alleles encoding 4CMenB vaccine antigens. Some correlations between clonal complexes and variants of examined proteins/BAST profiles were revealed and a high coverage of 4CMenB vaccine was estimated.
脑膜炎奈瑟菌 B 群（MenB）最近已成为波兰侵袭性脑膜炎奈瑟菌病的主要病因。因此，本研究的目的是通过 MLST 和编码 4CMenB 疫苗抗原的蛋白序列分析，对 2010-2016 年侵袭性脑膜炎奈瑟菌分离株进行特征描述。采用了两种覆盖度估计方法：波兰脑膜炎奈瑟菌 2010-2011 年的 MATS 结果外推（exMATS）和 gMATS，该方法结合了基因分型和 MATS 结果。在 662 株分离株中检测到 20 个克隆复合体（CC），其中最常见的是 CC32、CC41/44 和 CC18，分别占 31.9%、16.5%和 12.7%。共发现 111 种 PorA 可变区（VR1/VR2）组合，其中 P1.7,16（15.0%）和 P1.22,14（13.6%）较为常见。VR2:4 型疫苗变体在 7.3%的分离株中被检测到，主要代表 CC41/44 和非定型 CC。共发现 85 种 fHbp 等位基因，编码 74 种肽亚变种。作为 4CMenB 成分的亚变种 1.1 较为流行（24.2%），主要存在于 CC32 中。对 nhba 基因进行分型显示有 102 种等位基因编码 87 种肽。最常见的是肽 3（22.4%），而疫苗肽 2 则检出 9.8%，主要存在于 CC41/44 中。NadA 基因在 34.0%的分离株中被检测到，最常见的是肽 1（NadA-1 变体；71.6%），几乎仅存在于 CC32 脑膜炎奈瑟菌中。疫苗肽 8（NadA-2/3 变体）仅检出 1 次。因此，共揭示了 292 个完整的 BAST 图谱。关于疫苗覆盖度，39.7%的分离株至少有一种 4CMenB 疫苗变体，但根据 exMATS 和 gMATS，疫苗覆盖度分别为 83.3%和 86.6%。总之，根据 MLST 和编码 4CMenB 疫苗抗原的基因等位基因，波兰 MenB（2010-2016 年）具有高度多样性。揭示了某些克隆复合体和所研究蛋白/BAST 图谱变体之间的相关性，并估计了 4CMenB 疫苗的高覆盖率。
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