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Diversification in immunogenicity genes caused by selective pressures in invasive meningococci
Philip H C Kremer1, John A Lees2,3, Bart Ferwerda1
1Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscienc, Amsterdam, The Netherlands.
Microbial Genomics
|August 11, 2020
Summary
Population genomics of Neisseria meningitidis revealed a ST-41/44 sub-lineage expansion during a serogroup B meningitis hyperendemic period. This expansion, marked by specific antigen alleles, showed decreased 4CMenB vaccine coverage post-hyperendemic period.
Area of Science:
- Microbiology
- Genomics
- Epidemiology
Background:
- Neisseria meningitidis causes meningitis, with serogroup B historically leading to hyperendemic periods.
- Understanding meningococcal population dynamics is crucial for disease control and vaccine strategies.
Purpose of the Study:
- To investigate the population genomics of Neisseria meningitidis isolates in the Netherlands between 1979-2013.
- To evaluate the impact of a serogroup B invasive disease hyperendemic period on meningococcal strains.
- To identify genetic factors associated with specific meningococcal lineages and their relation to vaccine coverage.
Main Methods:
- Whole-genome sequencing of 486 Neisseria meningitidis isolates from distinct time periods (1979-2003 and 2006-2013).
- Population genetic analysis, including phylogenetic grouping and sequence typing (ST).
- Association analysis of antigen allele variants (FetA, FHbp, PorA, NHBA) with isolate characteristics and vaccine coverage.
Main Results:
- Serogroup B isolates were predominantly ST-41/44 (41%) and ST-32 complex (16%).
- A significant decrease in ST-41/44 complex sequences was observed after the decline of the serogroup B hyperendemic period (P=0.002).
- An expansion of a ST-41/44 sub-lineage, marked by four specific antigen allele variants, was associated with the hyperendemic period (P=0.014) and 4CMenB vaccine coverage (P<0.001).
- Isolates with lower predicted vaccine coverage clustered in different phylogenetic groups, trending towards the later time period (P=0.08).
Conclusions:
- A specific sub-lineage expansion within ST-41/44 complex Neisseria meningitidis correlated with a hyperendemic period of meningococcal meningitis.
- The expansion was characterized by distinct antigen peptide allele combinations, suggesting immune selection pressures.
- Preliminary evidence suggests a potential decrease in 4CMenB vaccine effectiveness or coverage in the post-hyperendemic era.
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