title: The impact of PEGylation on protein immunogenicity.
abstract: Covalent attachment of PEG (PEGylation) is widely used to improve the pharmaceutical properties of therapeutic proteins. The applicability and safety of this method have been proven by the use of various PEGylated pharmaceutical proteins approved by the Food and Drug Administration (FDA). One of the properties attributed to PEGylation is immunogenicity reduction of the PEGylated protein. In this study, the impact of PEGylation on immunogenicity was tested and compared for two proteins (chicken IgY and horse IgG) in two strains of mice (Balb/c and C57BL/6) for two routes of administration (i.v. and i.m.) and two sizes of PEG (5 kD and 20 kD). The influence of PEG was shown to be inconsistent between the mouse strains and routes of administration, even with the same tested protein. Consequently, immunogenicity reduction by PEGylation cannot be predicted or assumed; it must be tested on an individual case basis.
authors.affiliation: MIGAL, Galilee Technology Center, P.O. Box 831, Kiryat Shmona 11016, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Gefen
authors.forename: Jacob
authors.initials: J
authors.lastname: Vaya
authors.forename: Soliman
authors.initials: S
authors.lastname: Khatib
authors.forename: Natalia
authors.initials: N
authors.lastname: Harkevich
authors.forename: Fadi
authors.initials: F
authors.lastname: Artoul
authors.forename: E Dan
authors.initials: ED
authors.lastname: Heller
authors.forename: Jacob
authors.initials: J
authors.lastname: Pitcovski
authors.forename: Elina
authors.initials: E
authors.lastname: Aizenshtein
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002645:Chickens; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006736:Horses; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D007136:Immunoglobulins / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols; D011485:Protein Binding
chemical_list: D030161:Avian Proteins; D018985:Epitopes, B-Lymphocyte; C016512:IgY; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011092:Polyethylene Glycols