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Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development

BACKGROUND: Factor H binding protein (fHbp) is an important antigen for vaccines against meningococcal serogroup B disease. The protein binds human factor H (fH), which enables the bacteria to resist serum bactericidal activity. Little is known about the vaccine-potential of fHbp for control of meni...

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Autores principales: Pajon, Rolando, Fergus, Andrew M., Koeberling, Oliver, Caugant, Dominique A., Granoff, Dan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167780/
https://www.ncbi.nlm.nih.gov/pubmed/21909444
http://dx.doi.org/10.1371/journal.pntd.0001302
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author Pajon, Rolando
Fergus, Andrew M.
Koeberling, Oliver
Caugant, Dominique A.
Granoff, Dan M.
author_facet Pajon, Rolando
Fergus, Andrew M.
Koeberling, Oliver
Caugant, Dominique A.
Granoff, Dan M.
author_sort Pajon, Rolando
collection PubMed
description BACKGROUND: Factor H binding protein (fHbp) is an important antigen for vaccines against meningococcal serogroup B disease. The protein binds human factor H (fH), which enables the bacteria to resist serum bactericidal activity. Little is known about the vaccine-potential of fHbp for control of meningococcal epidemics in Africa, which typically are caused by non-group B strains. METHODOLOGY/PRINCIPAL FINDINGS: We investigated genes encoding fHbp in 106 serogroup A, W-135 and X case isolates from 17 African countries. We determined complement-mediated bactericidal activity of antisera from mice immunized with recombinant fHbp vaccines, or a prototype native outer membrane vesicle (NOMV) vaccine from a serogroup B mutant strain with over-expressed fHbp. Eighty-six of the isolates (81%) had one of four prevalent fHbp sequence variants, ID 4/5 (serogroup A isolates), 9 (W-135), or 74 (X) in variant group 1, or ID 22/23 (W-135) in variant group 2. More than one-third of serogroup A isolates and two-thirds of W-135 isolates tested had low fHbp expression while all X isolates tested had intermediate or high expression. Antisera to the recombinant fHbp vaccines were generally bactericidal only against isolates with fHbp sequence variants that closely matched the respective vaccine ID. Low fHbp expression also contributed to resistance to anti-fHbp bactericidal activity. In contrast to the recombinant vaccines, the NOMV fHbp ID 1 vaccine elicited broad anti-fHbp bactericidal activity, and the antibodies had greater ability to inhibit binding of fH to fHbp than antibodies elicited by the control recombinant fHbp ID 1 vaccine. CONCLUSION/SIGNIFICANCE: NOMV vaccines from mutants with increased fHbp expression elicit an antibody repertoire with greater bactericidal activity than recombinant fHbp vaccines. NOMV vaccines are promising for prevention of meningococcal disease in Africa and could be used to supplement coverage conferred by a serogroup A polysaccharide-protein conjugate vaccine recently introduced in some sub-Saharan countries.
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spelling pubmed-31677802011-09-09 Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development Pajon, Rolando Fergus, Andrew M. Koeberling, Oliver Caugant, Dominique A. Granoff, Dan M. PLoS Negl Trop Dis Research Article BACKGROUND: Factor H binding protein (fHbp) is an important antigen for vaccines against meningococcal serogroup B disease. The protein binds human factor H (fH), which enables the bacteria to resist serum bactericidal activity. Little is known about the vaccine-potential of fHbp for control of meningococcal epidemics in Africa, which typically are caused by non-group B strains. METHODOLOGY/PRINCIPAL FINDINGS: We investigated genes encoding fHbp in 106 serogroup A, W-135 and X case isolates from 17 African countries. We determined complement-mediated bactericidal activity of antisera from mice immunized with recombinant fHbp vaccines, or a prototype native outer membrane vesicle (NOMV) vaccine from a serogroup B mutant strain with over-expressed fHbp. Eighty-six of the isolates (81%) had one of four prevalent fHbp sequence variants, ID 4/5 (serogroup A isolates), 9 (W-135), or 74 (X) in variant group 1, or ID 22/23 (W-135) in variant group 2. More than one-third of serogroup A isolates and two-thirds of W-135 isolates tested had low fHbp expression while all X isolates tested had intermediate or high expression. Antisera to the recombinant fHbp vaccines were generally bactericidal only against isolates with fHbp sequence variants that closely matched the respective vaccine ID. Low fHbp expression also contributed to resistance to anti-fHbp bactericidal activity. In contrast to the recombinant vaccines, the NOMV fHbp ID 1 vaccine elicited broad anti-fHbp bactericidal activity, and the antibodies had greater ability to inhibit binding of fH to fHbp than antibodies elicited by the control recombinant fHbp ID 1 vaccine. CONCLUSION/SIGNIFICANCE: NOMV vaccines from mutants with increased fHbp expression elicit an antibody repertoire with greater bactericidal activity than recombinant fHbp vaccines. NOMV vaccines are promising for prevention of meningococcal disease in Africa and could be used to supplement coverage conferred by a serogroup A polysaccharide-protein conjugate vaccine recently introduced in some sub-Saharan countries. Public Library of Science 2011-09-06 /pmc/articles/PMC3167780/ /pubmed/21909444 http://dx.doi.org/10.1371/journal.pntd.0001302 Text en Pajon et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pajon, Rolando
Fergus, Andrew M.
Koeberling, Oliver
Caugant, Dominique A.
Granoff, Dan M.
Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development
title Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development
title_full Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development
title_fullStr Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development
title_full_unstemmed Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development
title_short Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development
title_sort meningococcal factor h binding proteins in epidemic strains from africa: implications for vaccine development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167780/
https://www.ncbi.nlm.nih.gov/pubmed/21909444
http://dx.doi.org/10.1371/journal.pntd.0001302
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