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Volume 6, Issue 9

Diversification in immunogenicity genes caused by selective pressures in invasive meningococci Open Access

Abstract

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): 4CMenB , antigens , evolution , genome sequencing and Neisseria meningitidis
Funding
This study was supported by the:
  • Rijksinstituut voor Volksgezondheid en Milieu
    • Principle Award Recipient: Arie van der Ende
  • Medical Research Foundation (Award 1365620)
    • Principle Award Recipient: John A Lees
  • Wellcome Trust (Award 098051)
    • Principle Award Recipient: Stephen D Bentley
  • ZonMw (Award 016.116.358)
    • Principle Award Recipient: Diederik van de Beek
  • H2020 European Research Council (Award 281156)
    • Principle Award Recipient: Diederik van de Beek
© 2020 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2020-08-10
2024-04-26
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Diversification in immunogenicity genes caused by selective pressures in invasive meningococci
M Gen 6, e000422 (2020); https://doi.org/10.1099/mgen.0.000422
/content/journal/mgen/10.1099/mgen.0.000422
/content/journal/mgen/10.1099/mgen.0.000422
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