National Reference Centre for Bacterial Meningitis, National Medicines Institute, Warsaw, Poland.
Institute Pasteur, Invasive Bacterial Infections Unit, Paris, France.
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。
