Meningococcal Factor H Binding Protein Vaccine Antigens with Increased Thermal Stability and Decreased Binding of Human Factor H

Rossi, Raffaella; Konar, Monica; Beernink, Peter T.

doi:10.1128/iai.01491-15

Cited by 15 publications

(23 citation statements)

References 42 publications

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“…Potential targets of these are the ligands of complement inhibitors made by bacteria; such that, if binding is prevented then complement activation would be expected to be promoted on the bacterial surface leading to its phagocytosis or lysis [48]. For example, recent progress has been made towards the development of a vaccine for N. meningitidis by targeting the factor H-binding protein fHbp [145]. Alternatively, engineered forms of FH might be used to elicit rapid and robust complement responses against specific pathogens.…”

Section: Factor H and Immune Evasionmentioning

confidence: 99%

Complement factor H in host defense and immune evasion

Parente

Clark

Inforzato

et al. 2016

Cell. Mol. Life Sci.

162

147

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Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

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Section: Factor H and Immune Evasionmentioning

confidence: 99%

Complement factor H in host defense and immune evasion

Parente

Clark

Inforzato

et al. 2016

Cell. Mol. Life Sci.

162

147

View full text Add to dashboard Cite

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“…5 , Panels E and F, respectively). Although we did not substitute the Cluster 2 residue K219 in the present study, the asparagine (N) substitution, K219N, did not decrease binding of JAR 31 in a related FHbp variant, ID 22, in recent study [37] or in FHbp ID 28 (R. Rossi and P.T. Beernink, unpublished data).…”

Section: Resultsmentioning

confidence: 52%

Molecular characterization of two sub-family specific monoclonal antibodies to meningococcal Factor H binding protein

Passo

Zippilli

Angiolillo

et al. 2018

Heliyon

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Factor H binding protein (FHbp) is a component of two licensed vaccines for prevention of sepsis and meningitis caused by serogroup B meningococci. FHbp binds human Factor H (FH), which contributes to evasion of host immunity and FHbp sequence variants can be classified into two sub-families. Antibodies against FHbp elicit complement-mediated killing and can inhibit recruitment of FH to the bacterial surface. We report epitope mapping studies of two murine IgG mAbs, designated JAR 31 and JAR 36, isolated from a mouse immunized with FHbp in sub-family A, which is present in ∼30–40% of invasive isolates. In the present study, we tested the reactivity of mAbs JAR 31 and JAR 36 with seven natural FHbp sequence variants from different phylogenic groups. We screened bacteriophage-displayed peptide libraries to identify amino acid residues contributing to the JAR 36 epitope. Based on the reactivities of mAbs JAR 31 and JAR 36 with the seven FHbp variants, and the frequent occurrences of aspartate (D) and lysine (K) residues in the JAR 36-bound phage peptides, we selected six residues in the carboxyl-terminal region of FHbp for replacement with alanine (A). The D201A and K203A substitutions respectively eliminated and decreased binding of mAbs JAR 31 and JAR 36 to FHbp. These substitutions did not affect binding of the control mAb JAR 33 or of human FH. JAR 31 or JAR 36 mediated cooperative complement-mediated bactericidal activity with other anti-FHbp mAbs. The identification of two amino acid residues involved in the epitopes recognized by these anti-FHbp mAbs may contribute to a more complete understanding of the spatial requirements for cooperative anti-FHbp mAb bactericidal activity.

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“…Gonococcal fHbp homologues (Jongerius et al 2013) and non-fH binding fHbp mutants (Beernink et al 2011) have been proposed as alternatives to circumvent the effect of human fH binding. There is preclinical evidence, for non-lipidated fHbp vaccines, that non-fH binding fHbp mutants can enhance immunogenicity compared with the corresponding wild type subvariant (Rossi et al 2016). However there have been no studies directly comparing these non-lipidated mutants with non-mutated, lipidated fHbp subvariants.…”

Section: Imd Contracting Autoimmune Disease As a Results Of Fhbp Exprementioning

confidence: 99%

The next chapter for group B meningococcal vaccines

Wang

Pollard²

2017

Critical Reviews in Microbiology

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The majority of invasive meningococcal disease (IMD) in the developed world is caused by capsular group B Neisseria meningitidis, however success with vaccination against organisms bearing this capsule has previously been restricted to control of geographically limited clonal outbreaks. As we enter a new era, with the first routine program underway to control endemic group B meningococcal disease for infants in the UK, it is timely to review the key landmarks in group B vaccine development, and discuss the issues determining whether control of endemic group B disease will be achieved. Evidence of a reduction in carriage acquisition of invasive group B meningococcal strains, after vaccination among adolescents, is imperative if routine immunization is to drive population control of disease beyond those who are vaccinated (i.e. through herd immunity). The need for multiple doses to generate a sufficiently protective response and reactogenicity remain significant problems with the new generation of vaccines. Despite these limitations, early data from the UK indicate that new group B meningococcal vaccines have the potential to have a major impact on meningococcal disease, and to provide new insight into how we might do better in the future.

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Meningococcal Factor H Binding Protein Vaccine Antigens with Increased Thermal Stability and Decreased Binding of Human Factor H

Cited by 15 publications

References 42 publications

Complement factor H in host defense and immune evasion

Complement factor H in host defense and immune evasion

Molecular characterization of two sub-family specific monoclonal antibodies to meningococcal Factor H binding protein

The next chapter for group B meningococcal vaccines

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