Factor H binding proteins (fHBP), are bacterial surface proteins currently undergoing human clinical trials as candidate serogroup B Neisseria meningitidis (MnB) vaccines. fHBP protein sequences segregate into two distinct subfamilies, designated A and B. Here, we report the specificity and vaccine potential of mono- or bivalent fHBP-containing vaccines. A bivalent fHBP vaccine composed of a member of each subfamily elicited substantially broader bactericidal activity against MnB strains expressing heterologous fHBP than did either of the monovalent vaccines. Bivalent rabbit immune sera tested in serum bactericidal antibody assays (SBAs) against a diverse panel of MnB clinical isolates killed 87 of the 100 isolates. Bivalent human immune sera killed 36 of 45 MnB isolates tested in SBAs. Factors such as fHBP protein variant, PorA subtype, or MLST were not predictive of whether the MnB strain could be killed by rabbit or human immune sera. Instead, the best predictor for killing in the SBA was the level of in vitro surface expression of fHBP. The bivalent fHBP vaccine candidate induced immune sera that killed MnB isolates representing the major MLST complexes, prevalent PorA subtypes, and fHBP variants that span the breadth of the fHBP phylogenetic tree. Importantly, epidemiologically prevalent fHBP variants from both subfamilies were killed.
%0 Journal Article
%1 jiang_broad_2010
%A Jiang, Han-Qing
%A Hoiseth, Susan K.
%A Harris, Shannon L.
%A McNeil, Lisa K.
%A Zhu, Duzhang
%A Tan, Cuiwen
%A Scott, Adrienne A.
%A Alexander, Kristin
%A Mason, Kathryn
%A Miller, Lynn
%A DaSilva, Ida
%A Mack, Michelle
%A Zhao, Xiao-Juan
%A Pride, Michael W.
%A Andrew, Lubomira
%A Murphy, Ellen
%A Hagen, Michael
%A French, Roger
%A Arora, Ashoni
%A Jones, Thomas R.
%A Jansen, Kathrin U.
%A Zlotnick, Gary W.
%A Anderson, Annaliesa S.
%D 2010
%J Vaccine
%K B, N. Vaccine meningitidis serogroup {LP2086,} {fHBP,}
%N 37
%P 6086--6093
%R 10.1016/j.vaccine.2010.06.083
%T Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease
%U http://www.sciencedirect.com/science/article/B6TD4-50GCK93-2/2/f2b1df6ec153a784641eafab633b8ac6
%V 28
%X Factor H binding proteins (fHBP), are bacterial surface proteins currently undergoing human clinical trials as candidate serogroup B Neisseria meningitidis (MnB) vaccines. fHBP protein sequences segregate into two distinct subfamilies, designated A and B. Here, we report the specificity and vaccine potential of mono- or bivalent fHBP-containing vaccines. A bivalent fHBP vaccine composed of a member of each subfamily elicited substantially broader bactericidal activity against MnB strains expressing heterologous fHBP than did either of the monovalent vaccines. Bivalent rabbit immune sera tested in serum bactericidal antibody assays (SBAs) against a diverse panel of MnB clinical isolates killed 87 of the 100 isolates. Bivalent human immune sera killed 36 of 45 MnB isolates tested in SBAs. Factors such as fHBP protein variant, PorA subtype, or MLST were not predictive of whether the MnB strain could be killed by rabbit or human immune sera. Instead, the best predictor for killing in the SBA was the level of in vitro surface expression of fHBP. The bivalent fHBP vaccine candidate induced immune sera that killed MnB isolates representing the major MLST complexes, prevalent PorA subtypes, and fHBP variants that span the breadth of the fHBP phylogenetic tree. Importantly, epidemiologically prevalent fHBP variants from both subfamilies were killed.
@article{jiang_broad_2010,
abstract = {Factor H binding proteins {(fHBP),} are bacterial surface proteins currently undergoing human clinical trials as candidate serogroup B Neisseria meningitidis {(MnB)} vaccines. {fHBP} protein sequences segregate into two distinct subfamilies, designated A and B. Here, we report the specificity and vaccine potential of mono- or bivalent {fHBP-containing} vaccines. A bivalent {fHBP} vaccine composed of a member of each subfamily elicited substantially broader bactericidal activity against {MnB} strains expressing heterologous {fHBP} than did either of the monovalent vaccines. Bivalent rabbit immune sera tested in serum bactericidal antibody assays {(SBAs)} against a diverse panel of {MnB} clinical isolates killed 87 of the 100 isolates. Bivalent human immune sera killed 36 of 45 {MnB} isolates tested in {SBAs.} Factors such as {fHBP} protein variant, {PorA} subtype, or {MLST} were not predictive of whether the {MnB} strain could be killed by rabbit or human immune sera. Instead, the best predictor for killing in the {SBA} was the level of in vitro surface expression of {fHBP.} The bivalent {fHBP} vaccine candidate induced immune sera that killed {MnB} isolates representing the major {MLST} complexes, prevalent {PorA} subtypes, and {fHBP} variants that span the breadth of the {fHBP} phylogenetic tree. Importantly, epidemiologically prevalent {fHBP} variants from both subfamilies were killed.},
added-at = {2011-03-11T10:05:34.000+0100},
author = {Jiang, {Han-Qing} and Hoiseth, Susan K. and Harris, Shannon L. and {McNeil}, Lisa K. and Zhu, Duzhang and Tan, Cuiwen and Scott, Adrienne A. and Alexander, Kristin and Mason, Kathryn and Miller, Lynn and {DaSilva}, Ida and Mack, Michelle and Zhao, {Xiao-Juan} and Pride, Michael W. and Andrew, Lubomira and Murphy, Ellen and Hagen, Michael and French, Roger and Arora, Ashoni and Jones, Thomas R. and Jansen, Kathrin U. and Zlotnick, Gary W. and Anderson, Annaliesa S.},
biburl = {https://www.bibsonomy.org/bibtex/2807be4c2aabe45abb05e1907f0733f53/jelias},
doi = {10.1016/j.vaccine.2010.06.083},
interhash = {b4314b406bac87b6de20b6ab86f6135f},
intrahash = {807be4c2aabe45abb05e1907f0733f53},
issn = {{0264-410X}},
journal = {Vaccine},
keywords = {B, N. Vaccine meningitidis serogroup {LP2086,} {fHBP,}},
month = aug,
number = 37,
pages = {6086--6093},
timestamp = {2011-03-11T10:06:23.000+0100},
title = {Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease},
url = {http://www.sciencedirect.com/science/article/B6TD4-50GCK93-2/2/f2b1df6ec153a784641eafab633b8ac6},
volume = 28,
year = 2010
}