ORAL IMMUNIZATION WITH POLY-(D,L-LACTIDE-CO-GLYCOLIDE) AND POLY-(L-LACTIC ACID) MICROSPHERES CONTAINING PNEUMOTROPIC BACTERIAL-ANTIGENS

Encouraged by recent findings showing the usefulness of nonreplicating antigen delivery systems in the induction of mucosal immune responses , we investigated microspheres as a means to deliver LW 50020, an immu nomodulator consisting of lysates of seven common respiratory pathogen s. BALB/c mice were orally immunized with LW 50020 encapsulated into p oly-(D, L-lactide-co-glycolide) (PLG) and poly-(L-lactic acid) (PLA) m icrospheres prepared by either a solvent-evaporation or a solvent-extr action double-emulsion technique. Particle uptake into intestinal Feve r's patches, induction of antibodies in sera and secretion of immunogl obulins by isolated Peyer's patches, lungs and spleen lymphocytes were investigated. Our results revealed size and surface characteristic-de pendent uptake of microspheres into Peyer's patches. Microsphere trans location into Fever's patches was efficient for 0.8-mu m microspheres, but poor for 2.0-mu m and surface-modified microspheres. We showed an enhanced immune response in the lungs and sera following oral immuniz ation with 0.8-mu m PLG solvent-evaporation microspheres. The immunomo dulation was statistically significant as compared to free LW 50020. I n contrast, oral immunization with other preparations caused reduced o r absent modulation of the immune response compared to 0.8-mu m micros pheres and free antigen. These findings indicate that microspheres dis playing small particle sizes, rapid antigen release and high antigen c ontent provide optimal tools to deliver orally applied antigens.