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TitleStructural basis for cooperativity of human monoclonal antibodies to meningococcal factor H-binding protein.
Journal, issue, pagesCommun Biol, Vol. 2, Page 241, Year 2019
Publish dateJun 26, 2019
AuthorsIlaria Peschiera / Maria Giuliani / Fabiola Giusti / Roberto Melero / Eugenio Paccagnini / Danilo Donnarumma / Werner Pansegrau / José M Carazo / Carlos O S Sorzano / Maria Scarselli / Vega Masignani / Lassi J Liljeroos / Ilaria Ferlenghi /
PubMed AbstractMonoclonal antibody (mAb) cooperativity is a phenomenon triggered when mAbs couples promote increased bactericidal killing compared to individual partners. Cooperativity has been deeply investigated ...Monoclonal antibody (mAb) cooperativity is a phenomenon triggered when mAbs couples promote increased bactericidal killing compared to individual partners. Cooperativity has been deeply investigated among mAbs elicited by factor H-binding protein (fHbp), a surface-exposed lipoprotein and one of the key antigens included in both serogroup B meningococcus vaccine Bexsero and Trumenba. Here we report the structural and functional characterization of two cooperative mAbs pairs isolated from Bexsero vaccines. The 3D electron microscopy structures of the human mAb-fHbp-mAb cooperative complexes indicate that the angle formed between the antigen binding fragments (fAbs) assume regular angle and that fHbp is able to bind simultaneously and stably the cooperative mAbs pairs and human factor H (fH) in vitro. These findings shed light on molecular basis of the antibody-based mechanism of protection driven by simultaneous recognition of the different epitopes of the fHbp and underline that cooperativity is crucial in vaccine efficacy.
External linksCommun Biol / PubMed:31263785 / PubMed Central
MethodsEM (single particle)
Resolution23.0 - 28.0 Å
Structure data

EMDB-4713:
Negative staining of antibodies cooperative complex formed by human fab7B10 and fab2C1 bound to the N. meningitidis antigen factor H binding protein (fHbp)
Method: EM (single particle) / Resolution: 23.0 Å

EMDB-4714:
Negative staining of antibodies cooperative complex formed by human IgG1 mAb7B10 and mAb2C1 bound to the N. meningitidis antigen factor H binding protein (fHbp)
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-4715:
Negative staining of antibodies cooperative complex formed by human IgG1 mAb1A3 and mAb1A12 bound to the N. meningitidis antigen factor H binding protein (fHbp)
Method: EM (single particle) / Resolution: 26.0 Å

Source
  • Homo sapiens (human)
  • Neisseria meningitidis serogroup B (bacteria)

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