Genomic analysis of Neisseria meningitidis strains causing invasive disease in Italy, 2018-2019

Neisseria meningitidis remains one of the leading causes of invasive disease worldwide, despite the availability of effective vaccines against the major capsular groups (i.e. serogroups A, B, C, W and Y). In this thesis, data from the National Surveillance System for Invasive Bacterial Diseases, active at the National Institute of Health (Istituto Superiore di Sanità, ISS), are presented. A comprehensive genotypic analysis, based primarily on whole-genome sequencing (WGS), was performed on the invasive meningococcal strains collected in Italy during 2018-2019. The resulting population structure was evaluated in light of the invasive meningococcal disease (IMD) epidemiological trends recorded between 2000 and 2019. WGS data were further screened to assess the variability of the protein antigens included in the vaccine formulations against serogroup B disease; then, in silico prediction of the likely immunological reactivity of the identified variants was carried out. Since protein antigens can be expressed independently of the capsular group, the analysis was conducted on both serogroup B and non-B strains. Epidemiological data confirmed the low incidence of IMD in Italy, even though in children under one year of age the incidence was one order of magnitude greater than the overall population. Throughout the 19-years period, the majority of cases were sporadic and mostly associated with serogroups B and C. Hyperinvasive/hypervirulent strains were found among meningococci circulating in 2018-2019 and clonal expansion events, not detectable through conventional typing, ii were noticed at the higher resolution afforded by core genome multilocus sequence typing (cgMLST). An extensive genetic diversity, involving also antigen-encoding genes, was observed in serogroup B meningococci. Despite this, the proportion of strains predicted to be likely susceptible to at least one of the two available vaccines against serogroup B disease was high. Based on genotypic predictors, putative reactivity to these vaccines appeared to be not restricted to serogroup B meningococci. Overall, the data underline the importance to depict the bacterial genomic diversity over time, in order to optimize IMD prevention and control through immunization by vaccination.