title: Influence of polymer hydrolysis on adjuvant effect of Gantrez®AN nanoparticles: implications for oral vaccination.
abstract: The adjuvant effect of methylvinylether-co-maleic anhydride (Gantrez®AN) nanoparticles was investigated during oral vaccination of mice with F4 adhesins of F4-positive Escherichia coli. To differentiate whether the adjuvant effect originated from a nanoparticle effect or a polymer effect, 20 μg F4 was administered as slightly crosslinked F4-containing nanoparticles (g(F4)(0.01)) or as F4 mixed with slightly crosslinked pure nanoparticles (F4+g(0.01)). The F4-specific immune response was reduced using F4-containing nanoparticles due to complete shielding of F4, whereas oral administration of F4+g(0.01) increased the level of F4-specific antibody-secreting cells (ASC) in the spleen. When repeating the vaccination study after 6months using freshly prepared nanoparticles, the adjuvant effect of F4+g(0.01) was lost due to an altered polymer reactivity caused by partial hydrolysis of anhydride groups of Gantrez®AN. Combining F4 with nanoparticles stabilised with a higher crosslinker amount during nanoparticle synthesis (F4+g(0.22)) could overcome the effect of partial polymer hydrolysis, as higher levels of ASC were detected. Hence, an in-depth characterisation of the Gantrez®AN polymer is required as stability issues can alter its biological effect during oral vaccination.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Vandamme
authors.forename: Vesna
authors.initials: V
authors.lastname: Melkebeek
authors.forename: Eric
authors.initials: E
authors.lastname: Cox
authors.forename: Peter
authors.initials: P
authors.lastname: Adriaensens
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Vlierberghe
authors.forename: Peter
authors.initials: P
authors.lastname: Dubruel
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000921:Antibody-Producing Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins / Q000276:immunology; D036781:Fimbriae Proteins / Q000276:immunology; D006868:Hydrolysis; D008298:Maleates / Q000008:administration & dosage* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D011145:Polyvinyls / Q000008:administration & dosage*; D013154:Spleen / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D029968:Escherichia coli Proteins; D008298:Maleates; D011108:Polymers; D011145:Polyvinyls; D014612:Vaccines; C058026:polyvinylmethoxyethylene-maleic anhydride copolymer; D036781:Fimbriae Proteins