Prevalence of Factor H–Binding Protein Variants and NadA among Meningococcal Group B Isolates from the United States: Implications for the Development of a Multicomponent Group B Vaccine

Beernink, Peter T.; Welsch, Jo Anne; Harrison, Lee H.; Leipus, Arunas; Kaplan, Sheldon L.; Granoff, Dan M.

doi:10.1086/514821

Cited by 54 publications

(65 citation statements)

References 40 publications

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“…Even the hyperinvasive ST32 complex, which is dominated by one subfamily B variant (B24, variant 1.1), contains at least 27 additional fHBP sequence variants (29). These results were also seen in other smaller, non-prevalence-based studies for MnB and in other N. meningitidis serogroups (32,112,113). Hao et al recently conducted a comparative analysis of 38 Neisseria genomes and found that MLST could not predict virulence gene content or strain phenotype (114).…”

Section: Heterogeneity Of Fhbp Variants Expressed With Common N Menimentioning

confidence: 98%

“…No SBA killing against the subfamily B isolate was observed using the subfamily A serum; however, some cross-protection was observed for the subfamily B vaccines and the subfamily A strains. Coverage studies for the nonlipidated variants have been further expanded and have demonstrated that as with lipidated proteins, SBA protection is subfamily specific; however, the breadth of coverage within the subfamily is not sufficiently covered when a single nonlipidated variant is used in the vaccine (20,31,113,118).…”

Section: Preclinical Evaluation Of the Potential Breadth Of Coverage mentioning

confidence: 99%

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Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

McNeil

Zagursky

Lin

et al. 2013

Microbiol Mol Biol Rev

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SUMMARY Neisseria meningitidis is a Gram-negative microorganism that exists exclusively in humans and can cause devastating invasive disease. Although capsular polysaccharide-based vaccines against serogroups A, C, Y, and W135 are widely available, the pathway to a broadly protective vaccine against serogroup B has been more complex. The last 11 years has seen the discovery and development of the N. meningitidis serogroup B (MnB) outer membrane protein factor H binding protein (fHBP) as a vaccine component. Since the initial discovery of fHBP, a tremendous amount of work has accumulated on the diversity, structure, and regulation of this important protein. fHBP has proved to be a virulence factor for N. meningitidis and a target for functional bactericidal antibodies. fHBP is critical for survival of meningococci in the human host, as it is responsible for the primary interaction with human factor H (fH). Binding of hfH by the meningococcus serves to downregulate the host alternative complement pathway and helps the organism evade host innate immunity. Preclinical studies have shown that an fHBP-based vaccine can elicit serum bactericidal antibodies capable of killing MnB, and the vaccine has shown very encouraging results in human clinical trials. This report reviews our current knowledge of fHBP. In particular, we discuss the recent advances in our understanding of fHBP, its importance to N. meningitidis , and its potential role as a vaccine for preventing MnB disease.

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Section: Heterogeneity Of Fhbp Variants Expressed With Common N Menimentioning

confidence: 98%

Section: Preclinical Evaluation Of the Potential Breadth Of Coverage mentioning

confidence: 99%

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

McNeil

Zagursky

Lin

et al. 2013

Microbiol Mol Biol Rev

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show abstract

“…However, it was not seen to contribute to SBA against other heterologous strains producing fHbp subvariants ID 14 (NZ98/254), ID 15 (M01 240101) or ID 4 (M01 242922), in contrast to the cross-reactive response seen in preclinical studies. 48,57 Expression levels of fHbp have been shown to dramatically affect SBA responses 43,57,58 but all except one of the test strains were shown to bind a murine antibody against this antigen. 33 The NadA component of the vaccine induced high levels of SBA against indicator strain 5/99 in agreement with preclinical data.…”

Section: Clinical Evaluationmentioning

confidence: 99%

Bexsero

Gorringe¹,

Pajón

2012

Human Vaccines & Immunotherapeutics

107

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“…However, some isolates are resistant to vaccine-induced SBA probably due to genetic variability of the antigen and/or low expression of the protein. 24 This vaccine is currently being evaluated in a Phase 1/2 trial.…”

Section: Other Protein-based Vaccinesmentioning

confidence: 99%

Meningococcal B vaccine development and evaluation of efficacy

Alphen¹,

Dobbelsteen²

2008

Human Vaccines

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Prevalence of Factor H–Binding Protein Variants and NadA among Meningococcal Group B Isolates from the United States: Implications for the Development of a Multicomponent Group B Vaccine

Abstract: Susceptibility to bactericidal activity can be predicted, in part, on the basis of fHBP phenotypes. Both vaccines have the potential to prevent most group B disease in the United States.

Cited by 54 publications

References 40 publications

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

Bexsero

Meningococcal B vaccine development and evaluation of efficacy

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