Encapsulation of antigen in poly(D,L-lactide-co-glycolide) microspheres protects from harmful effects of γ-irradiation as assessed in mice.
During the last two decades, synthetic polymers such as poly(lactide-co-glycolide) (PLGA) have been investigated for the development of nano- or microparticles as adjuvants or antigen vehicles. To enable transfer of this technology to human settings, the issue of sterilisation is of central importance. Since most polymers are heat-sensitive, sterilisation of polymeric microspheres for parenteral administration is assured either by costly and laborious aseptical preparation or the more preferred γ-irradiation. Many studies have investigated the effect of γ-irradiation on various physiochemical properties of the microspheres, but investigations on immunological effects are rare. We prepared poly(lactide-co-glycolide) (PLGA) microspheres containing ovalbumin (OVA) and tested the effect of γ-irradiation on the various immunological properties in mice. For reference, OVA was γ-irradiated and tested equivalently. The ability of encapsulated or non-encapsulated OVA to trigger activation of dendritic cells (DCs) was not affected by irradiation. However, while γ-irradiation of free OVA strongly influenced the antigen presentation, encapsulated OVA was not affected by irradiation. γ-Irradiation of OVA also reduced the immunogenicity in mice with regard to OVA-specific IgG1 production. In contrast, the antibody and the T-cell responses in mice immunised with PLGA-encapsulated OVA were similar irrespective of the γ-irradiation status. Hence, encapsulation of antigen into PLGA microspheres protects antigen from the potential detrimental effect of γ-irradiation leading to inactivation or altered immunogenicity. Sterilisation by γ-irradiation therefore enables a cost-effective production of PLGA-based antigen-delivery systems as compared to the more laborious and expensive aseptical production of such vaccines.
Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
Deepa
D
Mohanan
Bruno
B
Gander
Thomas M
TM
Kündig
Pål
P
Johansen
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D003362:Cost-Benefit Analysis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013242:Sterilization / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000191:economics / Q000276:immunology
D000941:Antigens; D007074:Immunoglobulin G; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin