Open AccessDiversification in immunogenicity genes caused by selective pressures in invasive meningococci
Author(s) -
Philip H. C. Kremer,
John Lees,
Bart Ferwerda,
Merijn W. Bijlsma,
Neil MacAlasdair,
Arie van der Ende,
Matthijs C. Brouwer,
Stephen D. Bentley,
Diederik van de Beek
Publication year - 2020
Publication title -
microbial genomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.476
H-Index - 28
ISSN - 2057-5858
DOI - 10.1099/mgen.0.000422
Subject(s) - immunogenicity , diversification (marketing strategy) , gene , biology , virology , genetics , immune system , business , marketing
We studied population genomics of 486 Neisseria meningitidis 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 ( P =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 ( P =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, P =0.0043 for FetA 1-5; P =0.0035 for FHbp 14; P =0.012 for PorA 7-2.4 and P =0.0031 for NHBA two peptide allele). These sequences were associated with 4CMenB vaccine coverage (Fisher's exact test, P <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 ( P =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.