Variability of genes encoding surface proteins used as vaccine antigens in meningococcal endemic and epidemic strain panels from Norway.

Surface-expressed protein antigens such as factor H-binding protein (fHbp), Neisserial adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and Porin protein A (PorA); all express sequence variability that can affect their function as protective immunogens when used in meningococcal serogroup B vaccines like the recently-approved 4CMenB (Bexsero(®)). We assessed the sequence variation of genes coding for these proteins and two additional proteins ("fusion partners" to fHbp and NHBA) in pathogenic isolates from a recent low incidence period (endemic situation; 2005-2006) in Norway. Findings among strains from this panel were contrasted to what was found among isolates from a historic outbreak (epidemic situation; 1985-1990). Multilocus sequence typing revealed 14 clonal complexes (cc) among the 66 endemic strains, while cc32 vastly predominated in the 38-strain epidemic panel. Serogroup B isolates accounted for 50/66 among endemic strains and 28/38 among epidemic strains. Potential strain-coverage ("sequence match") for the 4CMenB vaccine was identified among the majority (>70%) of the endemic serogroup B isolates and all of the epidemic serogroup B isolates evaluated. Further information about the degree of expression, surface availability and the true cross-reactivity for the vaccine antigens will be needed to fully characterize the clinical strain-coverage of 4CMenB in various geographic and epidemiological situations.