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The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B Neisseria meningitidis (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%). IMPORTANCE Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the Neisseria meningitidis strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B N. meningitidis strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease., (© Crown copyright 2020.)

Background: The epidemiology of invasive meningococcal disease (IMD) in Québec, Canada, has been dominated in the past decade by a clone of serogroup B (MenB) Neisseria meningitidis defined by multi-locus sequence typing (MLST) as sequence type (ST)-269. With the licensure of a new MenB vaccine Bexsero (4CMenB) in Canada, this study characterized invasive N. meningitidis recovered in Québec from 2009 to 2013, with an objective to examine the diversity of the 4CMenB vaccine antigens. Isolates were serogrouped by antisera and genogrouped by PCR, and further typed by whole cell ELISA for serotype and serosubtype antigens. Clonal analysis was done by MLST. Isolates were genotyped by analysis of their 4CMenB vaccine antigen genes of PorA, factor H binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA), and Neisseria Adhesin A (NadA)., Results: Of the 263 IMD isolates analysed, 229, 16, 10, 7, and 1 belonged to MenB, MenY, MenW, MenC, and MenX, respectively. Of the 229 MenB, 159 (69.4 %) were typed as ST-269 clonal complex (CC); and they possessed a restricted number of three fHbp and five nhba gene alleles. Nine N. meningitidis isolates (eight MenB and one MenY) were found to possess at least one gene that encoded for an antigen that matched exactly with protein variants in the 4CMenB vaccine. Two MenB expressed PorA antigen P1.4 and possessed the nhba gene for peptide 2; four other MenB were predicted to have NHBA peptide 2; another two MenB were predicted to encode fHbp peptide 1.1; and a single MenY was found to have nadA gene for NadA peptide 8. In addition, another 172 isolates were found to possess genes for variant 1 fHbp peptides other than peptide 1.1 or NadA variant 1-2/3 peptides other than peptide 8; and therefore, may potentially be covered by 4CMenB., Conclusion: The most prevalent clone of N. meningitidis in Quebec was ST-269 CC; and 96 % of the isolates in this CC were predicted to be covered by 4CMenB vaccine. Extensive genetic diversity was found in the other IMD isolates in Québec which might suggest a lower coverage by the vaccine when compared to the ST-269 MenB.

This study examined invasive Neisseria meningitidis recovered from invasive meningococcal disease (IMD) cases in Western Canada between 2009 and 2013. A total of 161 isolates from individual IMD cases were analysed for serogroup, serotype, serosubtype, PorA genotype, multi-locus sequence type and nucleotide sequence of their 4CMenB vaccine antigen genes. Sixty-nine isolates were serogroup B (MenB), 47 were serogroup Y (MenY), 22 were serogroup C (MenC), 19 were serogroup W (MenW), three were serogroup E and one was non-encapsulated. MenC, MenY and MenW were mainly clonal, represented primarily by clonal complex (cc) 11, cc23 or cc167, and cc22, respectively. In contrast, MenB were composed of eight different ccs together with 11 isolates not assigned to any known cc. Antigenic analysis and PorA genotyping confirmed the heterogeneity of MenB isolates, while such results supported the clonal nature of most MenC, MenY and MenW isolates. Thirty-four (21.1%) isolates had at least one gene that encoded one matching vaccine protein component of the 4CMenB vaccine (i.e. PorA P1.4; fHbp variant 1.1; NHBA peptide 2; and NadA-1, -2, or -3). An additional 18 isolates had genes that encoded variant 1 or subfamily B factor H binding proteins of this same vaccine., (© 2014 Public Health Agency of Canada.)

This study examined the antigenic and genetic diversity of serogroup B Neisseria meningitidis (MenB) recovered from invasive meningococcal disease (IMD) cases in Ontario, Canada, over the period 2001-2010 during which no MenB outbreaks had occurred. MenB was found to be responsible for 39 % of all IMD cases, with the remaining cases caused mainly by serogroups Y (28 %), C (23.5 %) and W135 (8 %). One hundred and ninety-three individual MenB case isolates were collected and characterized. Of the 88 sequence types (STs) identified, 75 were grouped into 14 known clonal complexes (CCs), whilst 13 STs were not assigned to any known CC. Fifty-seven different PorA genotypes and 88 STs defined the diversity of invasive MenB in Ontario, which supported the endemic nature of MenB disease in Ontario. Despite the presence of the hypervirulent ST-41/44 and ST-32 CCs, no single ST was predominant and responsible for a large number of IMD cases. Although the Québec outbreak clone of ST-269 was also found in Ontario, the 20 case isolates were genetically diverse: they grouped into seven STs and did not have a predominant PorA genotype. eburst analysis identified a new CC responsible for 14.5 % of the MenB case isolates. The six most common PorA variable region 2 (VR2) genotypes (VR2-9, -4, -14, -16, -13-1 and -16-3) were found in 67 % of invasive MenB isolates.