Sequence Diversity of the Factor H Binding Protein Vaccine Candidate in Epidemiologically Relevant Strains of Serogroup B Neisseria meningitidis

Ellen Murphy (1) , Lubomira Andrew (1) , Kwok-Leung Lee (1) , Deborah A. Dilts (1) , Lorna Nunez (1) , Pamela S. Fink (1) , Karita Ambrose (1) , Ray Borrow (2) , Jamie Findlow (2) , Muhamed-Kheir Taha (3) , Ala-Eddine Deghmane (3) , Paula Kriz (4) , Martin Musilek (4) , Jitka Kalmusova (4) , Dominique A. Caugant (5) , Torill Alvestad (5) , Leonard W. Mayer (6) , Claudio T. Sacchi (6, 7) , Xin Wang (6) , Diana Martin (8) , Anne von Gottberg (9) , Mignon Du Plessis (9) , Keith P. Klugman (10, 9) , Annaliesa S. Anderson (1) , Kathrin U. Jansen (1) , Gary W. Zlotnick (1) , Susan K. Hoiseth (1)

1 Wyeth Vaccines Research [Pearl River, NY]
2 Manchester Royal Infirmary
3 Infections Bactériennes Invasives - Invasive Bacterial Infections
4 National Institute of Public Health [Prague]
5 NIPH - Norwegian Institute of Public Health [Oslo]
6 CDC - Centers for Disease Control and Prevention [Atlanta]
7 Instituto Adolfo Lutz [São Paulo, Brazil]
8 ESR - Institute of Environmental Science and Research
9 NICD - National Institute for Communicable Diseases [Johannesburg]
10 Emory University [Atlanta, GA]

Background. Recombinant 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. Methods. Nucleotide 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. Results. Every 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. Conclusions. The 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.

Domains: Bacteriology

Ellen Murphy, Lubomira Andrew, Kwok-Leung Lee, Deborah A. Dilts, Lorna Nunez, et al.. Sequence Diversity of the Factor H Binding Protein Vaccine Candidate in Epidemiologically Relevant Strains of Serogroup B Neisseria meningitidis. Journal of Infectious Diseases, 2009, 200 (3), pp.379-389. ⟨10.1086/600141⟩. ⟨pasteur-03262212⟩