title: Prevention of human rhinovirus infection by multivalent fab molecules directed against ICAM-1.
abstract: We have developed a technology for improving avidity by making bivalent, trivalent, or tetravalent recombinant polypeptides. We designed tripartite proteins consisting of the Fab fragment of an antibody fused with a hinge derived from human immunoglobulin D that was further linked to polymerization domains derived from human coiled-coil proteins. We report here on the application of this method with a Fab domain directed against the major human rhinovirus receptor, intercellular adhesion molecule 1 (ICAM-1). Multivalent anti-ICAM-1 molecules were produced in bacteria and purified as soluble preassembled homogeneous proteins at high yield. These proteins successfully blocked rhinovirus infection in vitro, with the efficiency increasing from monomer to dimer, trimer, and tetramer. The diminished dissociation rate of these multivalent antibodies and their improved efficacy in preventing rhinovirus infection provide a foundation for producing prophylactic and therapeutic molecules against human rhinovirus, the causative agent of the majority of common colds.
authors.affiliation: Perlan Therapeutics, San Diego, California, USA.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Charles
authors.forename: Guang X
authors.initials: GX
authors.lastname: Luo
authors.forename: Lori A
authors.initials: LA
authors.lastname: Kohlstaedt
authors.forename: Ianessa G
authors.initials: IG
authors.lastname: Morantte
authors.forename: Elliott
authors.initials: E
authors.lastname: Gorfain
authors.forename: Linguang
authors.initials: L
authors.lastname: Cao
authors.forename: Jimmy H
authors.initials: JH
authors.lastname: Williams
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
mesh_terms: D000595:Amino Acid Sequence; D006367:HeLa Cells; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000502:physiology; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012229:Rhinovirus / Q000187:drug effects* / Q000502:physiology
chemical_list: D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1