scholarly journals Faculty Opinions recommendation of Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.

2011 ◽  
Author(s):  
Rino Rappuoli ◽  
Davide Serruto
Keyword(s):  
Neisseria Meningitidis ◽  
Virulence Factor ◽  
Binding Protein ◽  
Factor H ◽  
Vaccine Antigen

scholarly journals Characterization of Neisseria meningitidis Isolates That Do Not Express the Virulence Factor and Vaccine Antigen Factor H Binding Protein

2011 ◽  
Vol 18 (6) ◽  
pp. 1002-1014 ◽  
Author(s):  
Jay Lucidarme ◽  
Lionel Tan ◽  
Rachel M. Exley ◽  
Jamie Findlow ◽  
Ray Borrow ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Factor H ◽  
Negative Regulator ◽  
Vaccine Antigen ◽  
Natural Immunity ◽  
Content Type ◽  
Reading Frame ◽  
Flanking Sequences

ABSTRACTNeisseria meningitidisremains a leading cause of bacterial sepsis and meningitis. Complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. One approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor H (fH), to its surface via a lipoprotein, factor H binding protein (fHbp). Additionally, fHbp is a key antigen in vaccines currently being evaluated in clinical trials. Here we characterize strains ofN. meningitidisfrom several distinct clonal complexes which do not express fHbp; all strains were recovered from patients with disseminated meningococcal disease. We demonstrate that these strains have either a frameshift mutation in thefHbpopen reading frame or have entirely lostfHbpand some flanking sequences. No fH binding was detected to other ligands among thefHbp-negative strains. The implications of these findings for meningococcal pathogenesis and prevention are discussed.

scholarly journals Determination of serotyping antigens, clonal analysis and genetic characterization of the 4CMenB vaccine antigen genes in invasive Neisseria meningitidis from Western Canada, 2009 to 2013

2014 ◽  
Vol 63 (11) ◽  
pp. 1490-1499 ◽  
Author(s):  
Dennis K. S. Law ◽  
Jianwei Zhou ◽  
Saul Deng ◽  
Linda Hoang ◽  
Gregory Tyrrell ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Clonal Complex ◽  
Factor H ◽  
Vaccine Antigen ◽  
Western Canada ◽  
Antigenic Analysis ◽  
Clonal Nature ◽  
4Cmenb Vaccine

This study examined invasive Neisseria meningitidis recovered from invasive meningococcal disease (IMD) cases in Western Canada between 2009 and 2013. A total of 161 isolates from individual IMD cases were analysed for serogroup, serotype, serosubtype, PorA genotype, multi-locus sequence type and nucleotide sequence of their 4CMenB vaccine antigen genes. Sixty-nine isolates were serogroup B (MenB), 47 were serogroup Y (MenY), 22 were serogroup C (MenC), 19 were serogroup W (MenW), three were serogroup E and one was non-encapsulated. MenC, MenY and MenW were mainly clonal, represented primarily by clonal complex (cc) 11, cc23 or cc167, and cc22, respectively. In contrast, MenB were composed of eight different ccs together with 11 isolates not assigned to any known cc. Antigenic analysis and PorA genotyping confirmed the heterogeneity of MenB isolates, while such results supported the clonal nature of most MenC, MenY and MenW isolates. Thirty-four (21.1 %) isolates had at least one gene that encoded one matching vaccine protein component of the 4CMenB vaccine (i.e. PorA P1.4; fHbp variant 1.1; NHBA peptide 2; and NadA-1, -2, or -3). An additional 18 isolates had genes that encoded variant 1 or subfamily B factor H binding proteins of this same vaccine.

The vaccine antigen factor H binding protein from Neisseria meningitidis can be modified to reduce binding to factor H with no change in immunogenicity

2010 ◽  
Vol 61 (6) ◽  
pp. 516-517
Author(s):  
Lionel Tan ◽  
Joe Caesar ◽  
Yanwen Li ◽  
Rachel Exley ◽  
Elisabeth Kugelberg ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Factor H ◽  
Vaccine Antigen

scholarly journals Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen

2013 ◽  
Vol 110 (9) ◽  
pp. 3304-3309 ◽  
Author(s):  
Enrico Malito ◽  
Agnese Faleri ◽  
Paola Lo Surdo ◽  
Daniele Veggi ◽  
Giulietta Maruggi ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Binding Protein ◽  
Protein A ◽  
Factor H ◽  
Vaccine Antigen ◽  
Protective Epitope

Epitope Mapping of a Bactericidal Monoclonal Antibody against the Factor H Binding Protein of Neisseria meningitidis

2009 ◽  
Vol 386 (1) ◽  
pp. 97-108 ◽  
Author(s):  
Maria Scarselli ◽  
Francesca Cantini ◽  
Laura Santini ◽  
Daniele Veggi ◽  
Sara Dragonetti ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Neisseria Meningitidis ◽  
Epitope Mapping ◽  
Binding Protein ◽  
Factor H

scholarly journals Characterization of Diverse Subvariants of the Meningococcal Factor H (fH) Binding Protein for Their Ability To Bind fH, To Mediate Serum Resistance, and To Induce Bactericidal Antibodies

2010 ◽  
Vol 79 (2) ◽  
pp. 970-981 ◽  
Author(s):  
Kate L. Seib ◽  
Brunella Brunelli ◽  
Barbara Brogioni ◽  
Emmanuelle Palumbo ◽  
Stefania Bambini ◽  
...  
Keyword(s):  
Binding Protein ◽  
Genetically Engineered ◽  
Factor H ◽  
Serum Resistance ◽  
Dependent Manner ◽  
Bacterial Surface ◽  
Bactericidal Antibody ◽  
Human Sera ◽  
The Stability

ABSTRACTNeisseria meningitidisis a commensal of the human nasopharynx but is also a major cause of septicemia and meningitis. The meningococcal factor H binding protein (fHbp) binds human factor H (fH), enabling downregulation of complement activation on the bacterial surface. fHbp is a component of two serogroup B meningococcal vaccines currently in clinical development. Here we characterize 12 fHbp subvariants for their level of surface exposure and ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. Flow cytometry and Western analysis revealed that all strains examined expressed fHbp on their surface to different extents and bound fH in an fHbp-dependent manner. However, differences in fH binding did not always correlate with the level of fHbp expression, indicating that this is not the only factor affecting the amount of fH bound. To overcome the issue of strain variability in fHbp expression, the MC58ΔfHbpstrain was genetically engineered to express different subvariants from a constitutive heterologous promoter. These recombinant strains were characterized for fH binding, and the data confirmed that each subvariant binds different levels of fH. Surface plasmon resonance revealed differences in the stability of the fHbp-fH complexes that ranged over 2 orders of magnitude, indicating that differences in residues between and within variant groups can influence fH binding. Interestingly, the level of survival in human sera of recombinant MC58 strains expressing diverse subvariants did not correlate with the level of fH binding, suggesting that the interaction of fHbp with fH is not the only function of fHbp that influences serum resistance. Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response.

Prevalence of factor H Binding Protein sub-variants among Neisseria meningitidis in China

Vaccine ◽  
2017 ◽  
Vol 35 (18) ◽  
pp. 2343-2350 ◽  
Author(s):  
Fenglin Shi ◽  
Aiyu Zhang ◽  
Bingqing Zhu ◽  
Yuan Gao ◽  
Li Xu ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Factor H

scholarly journals Impaired Immunogenicity of a Meningococcal Factor H-Binding Protein Vaccine Engineered To Eliminate Factor H Binding

2010 ◽  
Vol 17 (7) ◽  
pp. 1074-1078 ◽  
Author(s):  
Peter T. Beernink ◽  
Jutamas Shaughnessy ◽  
Sanjay Ram ◽  
Dan M. Granoff
Keyword(s):  
Binding Protein ◽  
Factor H ◽  
Vaccine Antigen ◽  
Mouse Strains ◽  
Enzyme Linked Immunosorbent Assay ◽  
Complement Factor ◽  
Protein Vaccine ◽  
Wild Type ◽  
Bacterial Surface ◽  
Cast Doubt

ABSTRACT Meningococcal factor H-binding protein (fHbp) is a promising antigen that is part of two vaccines in clinical development. The protein specifically binds human complement factor H (fH), which downregulates complement activation on the bacterial surface and enables the organism to evade host defenses. In humans, the vaccine antigen forms a complex with fH, which may affect anti-fHbp antibody repertoire and decrease serum bactericidal activity by covering important fHbp epitopes. In a recent study, fHbp residues in contact with fH were identified from a crystal structure. Two fHbp glutamate residues that mediated ion-pair interactions with fH were replaced with alanine, and the resulting E218A/E239A mutant no longer bound the fH fragment. In the present study, we generated the E218A/E239A mutant recombinant protein and confirmed the lack of fH binding. By enzyme-linked immunosorbent assay (ELISA), the mutant fHbp showed similar respective concentration-dependent inhibition of binding of four bactericidal anti-fHbp monoclonal antibodies (MAbs) to fHbp, compared with inhibition by the soluble wild-type protein. In two mouse strains, the mutant fHbp elicited up to 4-fold-lower IgG anti-fHbp antibody titers and up to 20-fold-lower serum bactericidal titers than those elicited by the wild-type fHbp vaccine. Thus, although introduction of the two alanine substitutions to eliminate fH binding did not appear to destabilize the molecule globally, the mutations resulted in decreased immunogenicity in mouse models in which neither the mutant nor the wild-type control vaccine bound fH. These results cast doubt on the vaccine potential in humans of this mutant fHbp.

Sign in / Sign up

Export Citation Format

Share Document