title: Mannosamine-biotin as a novel masking agent for coating IgG for immune response silencing and augmentation of antibody-antigen interaction.
abstract: A variety of protein-coating procedures are used to modify proteins' properties. The principle coating agent used is PEGylation, in which proteins are coated by conjunction to polyethylene glycol (PEG). In the present study, we describe a novel approach that makes use of small molecules with multifunctional groups as the protein-coating agent. The new coating molecule was produced by reacting two endogenous molecules, mannosamine and biotin, to form mannose-biotin adducts (MBA). hIgG was coated with MBA at various MBA/protein ratios. The immunogenicity of MBA-coated hIgG was tested in chickens. A dose-responsive effect of MBA/hIgG ratio on immune response suppression was detected, with an optimal masking effect at a 12:1 ratio. The immune response to MBA-coated hIgG was about eightfold lower than that to PEG-coated hIgG. MBA also increased antibody-antigen-binding affinity, and decreased recognition of the Fc domain of MBA-coated hIgG by Fc receptor and secondary antibodies. While the PEG molecule consists of inert repeating units of ethylene oxide with no additional functional group to allow for potentially desirable modifications, the MBA has several functional groups, including vicinal hydroxyls, which can easily be converted to active residues such as aldehydes or carboxyls. This may be of importance for developing passive immunizations or for achieving tolerance of the immune response to an immunogenic molecule or virus. In summary, we developed a new protein-coating molecule with the ability to mask foreign antigens and in the case of antibodies, to enhance activity.
authors.affiliation: MIGAL - Galilee Technology Center, Kiryat Shmona 11016, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Vaya
authors.forename: Elina
authors.initials: E
authors.lastname: Aizenshtein
authors.forename: Soliman
authors.initials: S
authors.lastname: Khatib
authors.forename: Tal
authors.initials: T
authors.lastname: Gefen
authors.forename: Michael
authors.initials: M
authors.lastname: Fassler
authors.forename: Ramadan
authors.initials: R
authors.lastname: Musa
authors.forename: Simi
authors.initials: S
authors.lastname: Krispel
authors.forename: Jacob
authors.initials: J
authors.lastname: Pitcovski
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D001710:Biotin / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D002645:Chickens; D004306:Dose-Response Relationship, Immunologic; D006595:Hexosamines / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D006595:Hexosamines; D007074:Immunoglobulin G; C008322:mannosamine; D011092:Polyethylene Glycols; D001710:Biotin