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Genetic variability of Polish serogroup B meningococci (2010-2016) including the 4CMenB vaccine component genes
Izabela Waśko1, Agnieszka Gołębiewska1, Marlena Kiedrowska1
1National Reference Centre for Bacterial Meningitis, National Medicines Institute, Warsaw, Poland.
Abstract:
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.
Insights
Neisseria meningitidis serogroup B (MenB) in Poland showed high diversity between 2010-2016. Multilocus Sequence Typing (MLST) and vaccine antigen gene sequencing revealed significant genetic variation, but estimated high coverage for the 4CMenB vaccine.
Area of Science:
- Microbiology
- Vaccinology
- Epidemiology
Background:
- Neisseria meningitidis serogroup B (MenB) is a leading cause of invasive meningococcal disease in Poland.
- Characterizing MenB isolates is crucial for understanding disease epidemiology and vaccine effectiveness.
Purpose of the Study:
- To genetically characterize MenB isolates from invasive meningococcal disease cases in Poland between 2010 and 2016.
- To assess the potential coverage of the 4-component meningococcal serogroup B (4CMenB) vaccine.
Main Methods:
- Multilocus Sequence Typing (MLST) was used to determine the genetic relatedness of MenB isolates.
- Sequencing of genes encoding key vaccine antigens (PorA, fHbp, NHBA, NadA) was performed.
- Two methods, extrapolation of MATS (exMATS) and combined genotyping and MATS (gMATS), were used for vaccine coverage estimation.
Main Results:
- Sixty-six MenB isolates yielded 20 clonal complexes (CCs), with CC32, CC41/44, and CC18 being most frequent.
- High diversity in PorA variable regions (111 combinations), fHbp alleles (85), and nhba alleles (102) was observed.
- Estimated 4CMenB vaccine coverage was high, with exMATS and gMATS predicting 83.3% and 86.6% coverage, respectively, despite only 39.7% of isolates carrying a direct vaccine variant.
Conclusions:
- Polish MenB isolates exhibit significant genetic diversity based on MLST and vaccine antigen profiles.
- Correlations were found between specific clonal complexes and variants of vaccine-targeted proteins.
- The 4CMenB vaccine is estimated to provide substantial coverage against circulating MenB strains in Poland during the study period.
