• Ellen Murphy, Lubomira Andrew, Kwok-Leung Lee, Deborah A Dilts, Lorna Nunez, Pamela S Fink, Karita Ambrose, Ray Borrow, Jamie Findlow, Muhamed-Kheir Taha, Ala-Eddine Deghmane, Paula Kriz, Martin Musilek, Jitka Kalmusova, Dominique A Caugant, Torill Alvestad, Leonard W Mayer, Claudio T Sacchi, Xin Wang, Diana Martin, Anne von Gottberg, Mignon du Plessis, Keith P Klugman, Annaliesa S Anderson, Kathrin U Jansen, Gary W Zlotnick, and Susan K Hoiseth.
• Wyeth Vaccines Research, Pearl River, New York 10965, USA.
• J. Infect. Dis. 2009 Aug 1; 200 (3): 379-89.

BackgroundRecombinant forms of Neisseria meningitidis human factor H binding protein (fHBP) are undergoing clinical trials in candidate vaccines against invasive meningococcal serogroup B disease. We report an extensive survey and phylogenetic analysis of the diversity of fhbp genes and predicted protein sequences in invasive clinical isolates obtained in the period 2000-2006.MethodsNucleotide sequences of fhbp genes were obtained from 1837 invasive N. meningitidis serogroup B (MnB) strains from the United States, Europe, New Zealand, and South Africa. Multilocus sequence typing (MLST) analysis was performed on a subset of the strains.ResultsEvery strain contained the fhbp gene. All sequences fell into 1 of 2 subfamilies (A or B), with 60%-75% amino acid identity between subfamilies and at least 83% identity within each subfamily. One fHBP sequence may have arisen via inter-subfamily recombination. Subfamily B sequences were found in 70% of the isolates, and subfamily A sequences were found in 30%. Multiple fHBP variants were detected in each of the common MLST clonal complexes. All major MLST complexes include strains in both subfamily A and subfamily B.ConclusionsThe diversity of strains observed underscores the importance of studying the distribution of the vaccine antigen itself rather than relying on common epidemiological surrogates such as MLST.

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