For both fHbp and NHBA, antigen peptides with high frequency in the sample were associated mostly with one or two ccs, the most diverse cc being cc41/44 for both antigens. In general each peptide had a similar proportion of coverage when found in strains belonging to different ccs, with the exception of the NHBA peptide 21 that was significantly more covered in cc269 than

in cc35, suggesting a bias in the level of antigen expression associated with the genetic diversity between the two ccs. Albeit strains harboring specific combinations of MLST and antigen genotype were consistently covered (e.g. cc32 and fHbp1.1; cc41/44 and fHbp1.4; cc41/44 and NHBA2) the AZD6738 cell line majority of genetic profiles had both strains covered and not covered, confirming that antigen genotyping, neither alone nor in combination with MLST, would be sufficient to predict vaccine strain coverage for all isolates. While our active population-based sentinel surveillance data provide the most comprehensive measurement IPI-145 of IMD in Canada, several limitations apply. MenB IMD is rare and the numbers in any given age group or province are small; therefore our ability to detect differences among subgroups is limited, and differences in strain coverage among age or geographic groups were not statistically significant. Approximately 20% of MenB cases in our data were confirmed by PCR only with no isolate available for testing. Additionally, IMPACT surveillance includes

primarily urban areas of Canada and may not be representative of remote or rural regions. The MATS provides a conservative estimate of vaccine coverage, which may be an underestimate [15] and [28]. Finally, although the nadA gene was found in 12 isolates (7%) in our study, only two (1%) expressed NadA with a RP above the PBT. Since expression of NadA is repressed in vitro,

but not in vivo, conditions, MATS may underestimate NadA’s contribution to vaccine strain coverage [29] and [30]. Our study characterizes the current MenB molecular epidemiology and provides a good estimate of the potential coverage of 4CMenB. Accurate post-implementation Megestrol Acetate surveillance and/or post-implementation effectiveness studies will be necessary to determine the true effectiveness of this new vaccine [31], taking into account the level of vaccine coverage in the population and any herd protection. We gratefully acknowledge the expert assistance provided by the IMPACT Monitor Liaison (Heather Samson), the IMPACT nurse monitors and staff of the IMPACT data center (Kim Marty, Wenli Zhang, Shu Yu Fan and Debbe Heayn), the National Microbiology Laboratory (Averil Henderson), the HPA laboratory Manchester, UK (Jay Lucidarme, Stefanie Gilchrist and Danielle Thompson) and our public Libraries health and infectious disease colleagues. We thank the Directors and staff of the provincial and territorial public health laboratories for providing the isolates for this study. Author contributions: J.A.