title: Anionic microparticles are a potent delivery system for recombinant antigens from Neisseria meningitidis serotype B.
abstract: The adsorption behavior of model proteins onto anionic poly(lactide-co-glycolide) (PLG) microparticles was evaluated. PLG microparticles were prepared by a w/o/w solvent evaporation process in the presence of the anionic surfactant dioctyl sodium sulfosuccinate (DSS). The effect of surfactant concentration and adsorption conditions on the adsorption efficiency and release rates in vitro was also studied. Subsequently, the microparticle formulation was tested to evaluate the efficacy of anionic microparticles as delivery systems for recombinant antigens from Neisseria meningitides type B (Men B), with and without CpG adjuvant. Protein (antigen) binding to anionic PLG microparticles was influenced by both electrostatic interaction and by other mechanisms, including hydrophobic attraction. The Men B antigens adsorbed efficiently onto anionic PLG microparticles and, following immunization in mice, induced potent enzyme-linked immunosorbent assay (ELISA) and serum bactericidal activity in comparison to alum-adsorbed formulations. These Men B antigens represent an attractive approach for vaccine development.
authors.affiliation: Chiron Vaccines Research, Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA. manmohan_singh@chiron.com
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Jina
authors.initials: J
authors.lastname: Kazzaz
authors.forename: James
authors.initials: J
authors.lastname: Chesko
authors.forename: Elawati
authors.initials: E
authors.lastname: Soenawan
authors.forename: Mildred
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: Marzia
authors.initials: M
authors.lastname: Giuliani
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Rino
authors.initials: R
authors.lastname: Rappouli
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
mesh_terms: D000276:Adjuvants, Immunologic; D000327:Adsorption; D000534:Alum Compounds; D000818:Animals; D000838:Anions; D000907:Antibodies, Bacterial / Q000032:analysis; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008863:Microspheres; D009113:Muramidase / Q000737:chemistry; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D010316:Particle Size; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D015610:Serum Bactericidal Test; D013386:Succinates; D013501:Surface-Active Agents; D013816:Thermodynamics
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000838:Anions; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D011994:Recombinant Proteins; D013386:Succinates; D013501:Surface-Active Agents; C041524:aluminum sulfate; D009113:Muramidase; C024599:thiosuccinic acid