title: A two-stage strategy for sterilization of poly(lactide-co-glycolide) particles by γ-irradiation does not impair their potency for vaccine delivery.
abstract: This study evaluated the feasibility of using γ-irradiation for preparing sterile poly(lactide-co-glycolide) (PLG) formulations for vaccines. PLG microparticles were prepared by water-in-oil-in-water double-emulsion technique and lyophilized. The vials were γ-irradiated for sterilization process. Antigens from Neisseria meningitidis were adsorbed onto the surface of the particles and were characterized for protein adsorption. Antigens adsorbed onto the surface of the irradiated particles within 30 min. Mice were immunized with these formulations, and vaccine potency was measured as serum bactericidal titers. The γ-irradiated PLG particles resulted in equivalent serum bactericidal titers against a panel of five N. meningitidis strains as the nonirradiated PLG particles. The use of PLG polymers with different molecular weights did not influence the vaccine potency. The PLG particles prepared by γ-irradiation of the lyophilized formulations replace the need for aseptic manufacturing of vaccine formulations. This approach may enable the use of PLG formulations with a variety of antigens and stockpiling for pandemics.
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Jain
authors.forename: Padma
authors.initials: P
authors.lastname: Malyala
authors.forename: Michele
authors.initials: M
authors.lastname: Pallaoro
authors.forename: Marzia
authors.initials: M
authors.lastname: Giuliani
authors.forename: Holger
authors.initials: H
authors.lastname: Petersen
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
mesh_terms: D000327:Adsorption; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D005612:Freeze Drying; D005720:Gamma Rays; D007114:Immunization; D019344:Lactic Acid / Q000737:chemistry*; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013242:Sterilization / Q000379:methods*
chemical_list: D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid