Single dose, polymeric, microparticle-based vaccines: the influence of formulation conditions on the magnitude and duration of the immune response to a protein antigen.
Ovalbumin-loaded poly (D,L-lactide co-glycolide) [OVA-loaded PLG] microparticles, produced by emulsion/solvent evaporation stimulated the production of high serum IgG antibody levels after a single subcutaneous (s.c.) administration in mice and the duration of the immune response paralleled the degradation rate of the carrier. Formulations based on slow resorbing PLG maintained relatively constant peak antibody levels for 26 weeks and high titres for over 1 year at a level approximating the peak response to the faster resorbing, OVA-loaded particles which was of lower duration. Vaccine formulations prepared by simple mixing of blank PLG microparticles and OVA exhibited low primary immune responses which were only elevated by boosting. OVA-loaded PLG microparticles exhibited a substantial surface protein component amounting to ca 40% and 60% of the total protein loading for slow resorbing and fast resorbing PLG, respectively. These findings suggest that sustained presentation of surface protein to the immune system was a major factor in the induction and long-term maintenance of high antibody titres following a single s.c. administration of OVA-loaded microparticles.
Coombes
A G
AG
Department of Pharmaceutical Sciences, University of Nottingham, University Park, UK.
Lavelle
E C
EC
Jenkins
P G
PG
Davis
S S
SS
D000534:Alum Compounds; D000818:Animals; D000906:Antibodies / Q000097:blood*; D001672:Biocompatible Materials; D004337:Drug Carriers; D007074:Immunoglobulin G / Q000097:blood*; D019344:Lactic Acid; D051379:Mice; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D014612:Vaccines / Q000008:administration & dosage*
D000534:Alum Compounds; D000906:Antibodies; D001672:Biocompatible Materials; D004337:Drug Carriers; D007074:Immunoglobulin G; D011108:Polymers; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C041524:aluminum sulfate; D010047:Ovalbumin