title: Cross-neutralizing human anti-poliovirus antibodies bind the recognition site for cellular receptor.
abstract: Most structural information about poliovirus interaction with neutralizing antibodies was obtained in the 1980s in studies of mouse monoclonal antibodies. Recently we have isolated a number of human/chimpanzee anti-poliovirus antibodies and demonstrated that one of them, MAb A12, could neutralize polioviruses of both serotypes 1 and 2. This communication presents data on isolation of an additional cross-neutralizing antibody (F12) and identification of a previously unknown epitope on the surface of poliovirus virions. Epitope mapping was performed by sequencing of antibody-resistant mutants and by cryo-EM of complexes of virions with Fab fragments. The results have demonstrated that both cross-neutralizing antibodies bind the site located at the bottom of the canyon surrounding the fivefold axis of symmetry that was previously shown to interact with cellular poliovirus receptor CD155. However, the same antibody binds to serotypes 1 and 2 through different specific interactions. It was also shown to interact with type 3 poliovirus, albeit with about 10-fold lower affinity, insufficient for effective neutralization. Antibody interaction with the binding site of the cellular receptor may explain its broad reactivity and suggest that further screening or antibody engineering could lead to a universal antibody capable of neutralizing all three serotypes of poliovirus.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Zhaochun
authors.initials: Z
authors.lastname: Chen
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Fischer
authors.forename: Diana
authors.initials: D
authors.lastname: Kouiavskaia
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Hansen
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ludtke
authors.forename: Bella
authors.initials: B
authors.lastname: Bidzhieva
authors.forename: Michelle
authors.initials: M
authors.lastname: Makiya
authors.forename: Liane
authors.initials: L
authors.lastname: Agulto
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chumakov
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity / Q000276:immunology; D001483:Base Sequence; D002213:Capsid / Q000737:chemistry / Q000378:metabolism*; D061505:Cell Surface Display Techniques; D003429:Cross Reactions / Q000276:immunology*; D020285:Cryoelectron Microscopy; D060740:Disease Eradication / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017955:Poliovirus / Q000276:immunology*; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D000914:Antibodies, Viral
keywords: antiviral therapy; broadly reactive antibodies; passive immunization; phage display