Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis.
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.
Murphy
Ellen
E
Wyeth Vaccines Research, Pearl River, New York 10965, USA.
Andrew
Lubomira
L
Lee
Kwok-Leung
KL
Dilts
Deborah A
DA
Nunez
Lorna
L
Fink
Pamela S
PS
Ambrose
Karita
K
Borrow
Ray
R
Findlow
Jamie
J
Taha
Muhamed-Kheir
MK
Deghmane
Ala-Eddine
AE
Kriz
Paula
P
Musilek
Martin
M
Kalmusova
Jitka
J
Caugant
Dominique A
DA
Alvestad
Torill
T
Mayer
Leonard W
LW
Sacchi
Claudio T
CT
Wang
Xin
X
Martin
Diana
D
von Gottberg
Anne
A
du Plessis
Mignon
M
Klugman
Keith P
KP
Anderson
Annaliesa S
AS
Jansen
Kathrin U
KU
Zlotnick
Gary W
GW
Hoiseth
Susan K
SK
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005060:Europe / Q000453:epidemiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D014644:Genetic Variation; D006801:Humans; D008585:Meningitis, Meningococcal / Q000453:epidemiology / Q000382:microbiology*; D022401:Meningococcal Vaccines / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009520:New Zealand / Q000453:epidemiology; D013019:South Africa / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis