Diversification in immunogenicity genes caused by selective pressures in invasive meningococci

• Published in: Microbial genomics Vol. 6; no. 9
• Main Authors: Kremer, Philip H C, Lees, John A, Ferwerda, Bart, Bijlsma, Merijn W, MacAlasdair, Neil, van der Ende, Arie, Brouwer, Matthijs C, Bentley, Stephen D, van de Beek, Diederik
• Format: Journal Article
• Language: English
• Published: England Microbiology Society 01.09.2020
• Subjects: Adolescent; Antigens, Bacterial - genetics; Genetic Variation; Genome, Bacterial; Humans; Meningitis, Meningococcal - microbiology; Metagenomics; Mutation Rate; Neisseria meningitidis - classification; Neisseria meningitidis - genetics; Neisseria meningitidis - immunology; Neisseria meningitidis - isolation & purification; Netherlands; Phylogeny; Selection, Genetic; Whole Genome Sequencing - methods; Netherlands; genome sequencing; Neisseria meningitidis; 4CMenB; evolution; antigens
• ISSN: 2057-5858; 2057-5858
• DOI: 10.1099/mgen.0.000422

We studied population genomics of 486 isolates causing meningitis in the Netherlands during the period 1979-2003 and 2006-2013 using whole-genome sequencing to evaluate the impact of a hyperendemic period of serogroup B invasive disease. The majority of serogroup B isolates belonged to ST-41/44 (41 %) and ST-32 complex (16 %). Comparing the time periods, before and after the decline of serogroup B invasive disease, there was a decrease of ST-41/44 complex sequences ( =0.002). We observed the expansion of a sub-lineage within ST-41/44 complex sequences being associated with isolation from the 1979-2003 time period ( =0.014). Isolates belonging to this sub-lineage expansion within ST-41/44 complex were marked by four antigen allele variants. Presence of these allele variants was associated with isolation from the 1979-2003 time period after correction for multiple testing (Wald test, =0.0043 for FetA 1-5; =0.0035 for FHbp 14; =0.012 for PorA 7-2.4 and =0.0031 for NHBA two peptide allele). These sequences were associated with 4CMenB vaccine coverage (Fisher's exact test, <0.001). Outside of the sub-lineage expansion, isolates with markedly lower levels of predicted vaccine coverage clustered in phylogenetic groups showing a trend towards isolation in the 2006-2013 time period ( =0.08). In conclusion, we show the emergence and decline of a sub-lineage expansion within ST-41/44 complex isolates concurrent with a hyperendemic period in meningococcal meningitis. The expansion was marked by specific antigen peptide allele combinations. We observed preliminary evidence for decreasing 4CMenB vaccine coverage in the post-hyperendemic period.