Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates

Jane W. Marsh; Kathleen A. Shutt; Rolando Pajon; Mary M. Tulenko; Stephen Liu; Rosemary A. Hollick; Julia A. Kiehlbauch; Thomas A. Clark; David S. Stephens; Kathryn E. Arnold; Robert A. Myers; Leonard W. Mayer; Lee H. Harrison

doi:10.1016/j.vaccine.2011.06.025

Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates

Jane W. Marsh, Kathleen A. Shutt, Rolando Pajon, Mary M. Tulenko, Stephen Liu, Rosemary A. Hollick, Julia A. Kiehlbauch, Thomas A. Clark, David S. Stephens, Kathryn E. Arnold, Robert A. Myers, Leonard W. Mayer, Lee H. Harrison

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Several meningococcal vaccines under development for prevention of serogroup B disease target the factor H-binding protein (FHbp), an immunogenic lipoprotein expressed on the surface of Neisseria meningitidis. Based upon sequence and phylogenetic analyses, FHbp can be classified into 3 protein variants (1, 2 or 3) or 2 subfamilies (A or B). The potential effect of FHbp-containing vaccines on meningococcal carriage is not known. We determined the diversity of FHbp among a population of carriage isolates obtained from Georgia and Maryland high school students in 1998 and 2006-2007. Analysis of the fHbp gene sequence from 408 carriage isolates identified 30 different FHbp protein sequences. The majority of carriage isolates harbored FHbp proteins belonging to variant 2/subfamily A. Association between FHbp proteins and genetic lineage was observed among the carriage isolates. However, split decomposition analysis, together with tests of linkage disequilibrium and pairwise homoplasy suggest recombination at fHbp contribute to allelic diversity. Of note, the FHbp proteins in serogroup B vaccines under development are either absent or not well represented in this carriage population. The FHbp genetic repertoire observed in carriage isolate populations will be useful in understanding the potential impact of FHbp-containing vaccines on meningococcal carriage.

Original language	English (US)
Pages (from-to)	6049-6058
Number of pages	10
Journal	Vaccine
Volume	29
Issue number	35
DOIs	https://doi.org/10.1016/j.vaccine.2011.06.025
State	Published - Aug 11 2011

Keywords

FHbp
Genetic lineage
Meningococcal vaccine
Recombination

ASJC Scopus subject areas

Molecular Medicine
Immunology and Microbiology(all)
veterinary(all)
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2011.06.025

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@article{64c19b84d1ad436e903a106a871b7c29,

title = "Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates",

abstract = "Several meningococcal vaccines under development for prevention of serogroup B disease target the factor H-binding protein (FHbp), an immunogenic lipoprotein expressed on the surface of Neisseria meningitidis. Based upon sequence and phylogenetic analyses, FHbp can be classified into 3 protein variants (1, 2 or 3) or 2 subfamilies (A or B). The potential effect of FHbp-containing vaccines on meningococcal carriage is not known. We determined the diversity of FHbp among a population of carriage isolates obtained from Georgia and Maryland high school students in 1998 and 2006-2007. Analysis of the fHbp gene sequence from 408 carriage isolates identified 30 different FHbp protein sequences. The majority of carriage isolates harbored FHbp proteins belonging to variant 2/subfamily A. Association between FHbp proteins and genetic lineage was observed among the carriage isolates. However, split decomposition analysis, together with tests of linkage disequilibrium and pairwise homoplasy suggest recombination at fHbp contribute to allelic diversity. Of note, the FHbp proteins in serogroup B vaccines under development are either absent or not well represented in this carriage population. The FHbp genetic repertoire observed in carriage isolate populations will be useful in understanding the potential impact of FHbp-containing vaccines on meningococcal carriage.",

keywords = "FHbp, Genetic lineage, Meningococcal vaccine, Recombination",

author = "Marsh, {Jane W.} and Shutt, {Kathleen A.} and Rolando Pajon and Tulenko, {Mary M.} and Stephen Liu and Hollick, {Rosemary A.} and Kiehlbauch, {Julia A.} and Clark, {Thomas A.} and Stephens, {David S.} and Arnold, {Kathryn E.} and Myers, {Robert A.} and Mayer, {Leonard W.} and Harrison, {Lee H.}",

note = "Funding Information: This publication made use of the Neisseria Multi Locus Sequence Typing website ( http://pubmlst.org/neisseria/ ) developed by Keith Jolley and Man-Suen Chan located at the University of Oxford [44] . The development of this site has been funded by the Wellcome Trust and European Union. We also thank Dan Granoff and Maria Brooks for helpful discussions, and Scott Kellerman for his assistance with data from the 1998 Georgia carriage study and David Blythe and Pat Ryan for their support of this study. Funding Information: This study was supported in part by the Centers for Diseases Control and Prevention . Sanofi Pasteur supported the 2006–2007 meningococcal carriage study through a grant to the CDC Foundation. Funding Information: Dr. Harrison receives funding from the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. He receives research support and lecture fees from Sanofi Pasteur; lecture fees from Novartis Vaccines; and has served as a consultant to GlaxoSmithKline, Novartis Vaccines, Sanofi Pasteur, and Pfizer. Ms. Shutt and Dr. Marsh receive research support from Sanofi Pasteur. Dr. Stephens has research funding from the National Institute of Allergy and Infectious Diseases, the Department of Veterans Affairs and the Georgia Research Alliance. Other authors: no disclosures. ",

year = "2011",

month = aug,

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doi = "10.1016/j.vaccine.2011.06.025",

language = "English (US)",

volume = "29",

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AU - Marsh, Jane W.

AU - Shutt, Kathleen A.

AU - Pajon, Rolando

AU - Tulenko, Mary M.

AU - Liu, Stephen

AU - Hollick, Rosemary A.

AU - Kiehlbauch, Julia A.

AU - Clark, Thomas A.

AU - Stephens, David S.

AU - Arnold, Kathryn E.

AU - Myers, Robert A.

AU - Mayer, Leonard W.

AU - Harrison, Lee H.

N1 - Funding Information: This publication made use of the Neisseria Multi Locus Sequence Typing website ( http://pubmlst.org/neisseria/ ) developed by Keith Jolley and Man-Suen Chan located at the University of Oxford [44] . The development of this site has been funded by the Wellcome Trust and European Union. We also thank Dan Granoff and Maria Brooks for helpful discussions, and Scott Kellerman for his assistance with data from the 1998 Georgia carriage study and David Blythe and Pat Ryan for their support of this study. Funding Information: This study was supported in part by the Centers for Diseases Control and Prevention . Sanofi Pasteur supported the 2006–2007 meningococcal carriage study through a grant to the CDC Foundation. Funding Information: Dr. Harrison receives funding from the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. He receives research support and lecture fees from Sanofi Pasteur; lecture fees from Novartis Vaccines; and has served as a consultant to GlaxoSmithKline, Novartis Vaccines, Sanofi Pasteur, and Pfizer. Ms. Shutt and Dr. Marsh receive research support from Sanofi Pasteur. Dr. Stephens has research funding from the National Institute of Allergy and Infectious Diseases, the Department of Veterans Affairs and the Georgia Research Alliance. Other authors: no disclosures.

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N2 - Several meningococcal vaccines under development for prevention of serogroup B disease target the factor H-binding protein (FHbp), an immunogenic lipoprotein expressed on the surface of Neisseria meningitidis. Based upon sequence and phylogenetic analyses, FHbp can be classified into 3 protein variants (1, 2 or 3) or 2 subfamilies (A or B). The potential effect of FHbp-containing vaccines on meningococcal carriage is not known. We determined the diversity of FHbp among a population of carriage isolates obtained from Georgia and Maryland high school students in 1998 and 2006-2007. Analysis of the fHbp gene sequence from 408 carriage isolates identified 30 different FHbp protein sequences. The majority of carriage isolates harbored FHbp proteins belonging to variant 2/subfamily A. Association between FHbp proteins and genetic lineage was observed among the carriage isolates. However, split decomposition analysis, together with tests of linkage disequilibrium and pairwise homoplasy suggest recombination at fHbp contribute to allelic diversity. Of note, the FHbp proteins in serogroup B vaccines under development are either absent or not well represented in this carriage population. The FHbp genetic repertoire observed in carriage isolate populations will be useful in understanding the potential impact of FHbp-containing vaccines on meningococcal carriage.

AB - Several meningococcal vaccines under development for prevention of serogroup B disease target the factor H-binding protein (FHbp), an immunogenic lipoprotein expressed on the surface of Neisseria meningitidis. Based upon sequence and phylogenetic analyses, FHbp can be classified into 3 protein variants (1, 2 or 3) or 2 subfamilies (A or B). The potential effect of FHbp-containing vaccines on meningococcal carriage is not known. We determined the diversity of FHbp among a population of carriage isolates obtained from Georgia and Maryland high school students in 1998 and 2006-2007. Analysis of the fHbp gene sequence from 408 carriage isolates identified 30 different FHbp protein sequences. The majority of carriage isolates harbored FHbp proteins belonging to variant 2/subfamily A. Association between FHbp proteins and genetic lineage was observed among the carriage isolates. However, split decomposition analysis, together with tests of linkage disequilibrium and pairwise homoplasy suggest recombination at fHbp contribute to allelic diversity. Of note, the FHbp proteins in serogroup B vaccines under development are either absent or not well represented in this carriage population. The FHbp genetic repertoire observed in carriage isolate populations will be useful in understanding the potential impact of FHbp-containing vaccines on meningococcal carriage.

KW - FHbp

KW - Genetic lineage

KW - Meningococcal vaccine

KW - Recombination

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Diversity of factor H-binding protein in Neisseria meningitidis carriage isolates

Abstract

Keywords

ASJC Scopus subject areas

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