title: Polymer Structure and Conformation Alter the Antigenicity of Virus-like Particle-Polymer Conjugates.
abstract: Covalent conjugation of water-soluble polymers to proteins is critical for evading immune surveillance in the field of biopharmaceuticals. The most common and long-standing polymer modification is the attachment of methoxypoly(ethylene glycol) (mPEG), termed PEGylation, which has led to several clinically approved pharmaceuticals. Recent data indicate that brush-type polymers significantly enhance in vitro and in vivo properties. Herein, the polymer conformation of poly(ethylene glycol) is detailed and compared with those of water-soluble polyacrylate and polynorbornene (PNB) when attached to icosahedral virus-like particles. Small-angle neutron scattering reveals vastly different polymer conformations of the multivalent conjugates. Immune recognition of conjugated particles was evaluated versus PEGylated particles, and PNB conjugation demonstrated the most effective shielding from antibody recognition.
authors.forename: Parker W
authors.initials: PW
authors.lastname: Lee
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Isarov
authors.forename: Jaqueline D
authors.initials: JD
authors.lastname: Wallat
authors.forename: Sudheer K
authors.initials: SK
authors.lastname: Molugu
authors.forename: Sourabh
authors.initials: S
authors.lastname: Shukla
authors.forename: Jessie E P
authors.initials: JE
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Chemistry and Biochemistry, Miami University , Oxford, Ohio 45056, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lucius Dougherty
authors.affiliation: Department of Chemistry and Biochemistry, Miami University , Oxford, Ohio 45056, United States.
authors.forename: Dominik
authors.identifier: 0000-0002-3828-5481
authors.initials: D
authors.lastname: Konkolewicz
authors.forename: Phoebe L
authors.initials: PL
authors.lastname: Stewart
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
authors.forename: Michael J A
authors.identifier: 0000-0003-2571-2111
authors.initials: MJ
authors.lastname: Hore
authors.forename: Jonathan K
authors.identifier: 0000-0001-5869-6942
authors.initials: JK
authors.lastname: Pokorski
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D033363:Neutron Diffraction; D010969:Plastics / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D053838:Scattering, Small Angle; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry*
chemical_list: D000179:Acrylates; D010969:Plastics; D058425:Vaccines, Virus-Like Particle; C071464:polynorbornen; D011092:Polyethylene Glycols