TY - JOUR
T1 - Diversification in immunogenicity genes caused by selective pressures in invasive meningococci
AU - Kremer, Philip H. C.
AU - Lees, John A.
AU - Ferwerda, Bart
AU - Bijlsma, Merijn W.
AU - Macalasdair, Neil
AU - van der Ende, Arie
AU - Brouwer, Matthijs C.
AU - Bentley, Stephen D.
AU - van de Beek, Diederik
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - 4CMenB
KW - Antigens
KW - Evolution
KW - Genome sequencing
KW - Neisseria meningitidis
UR - http://www.scopus.com/inward/record.url?scp=85091715297&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85091715297&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/32776867
U2 - https://doi.org/10.1099/mgen.0.000422
DO - https://doi.org/10.1099/mgen.0.000422
M3 - Article
C2 - 32776867
SN - 2057-5858
VL - 6
SP - 1
EP - 9
JO - Microbial genomics
JF - Microbial genomics
IS - 9
M1 - 000422
ER -