| Autor: |
Savitskaya VY; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia., Dolinnaya NG; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia., Strekalovskikh VV; Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119234, Russia., Peskovatskova ES; Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119234, Russia., Snyga VG; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia., Trefilov VS; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119991, Russia., Monakhova MV; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119992, Russia., Kubareva EA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, Moscow 119992, Russia. |
| Abstrakt: |
Neisseria meningitidis ( N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and Random Forest Classifier machine learning methods, we estimated the potential strain coverage of fHbp and NHBA vaccine variants (51 and about 25%, respectively); the NadA antigen sequence was found in only 18% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden the coverage of N. meningitidis strains. |
