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 immunomodulator consisting of lysates of seven common respiratory pathogens. BALB/c mice were orally immunized with LW 50020 encapsulated into poly-(D, L-lactide-co-glycolide) (PLG) and poly-(L-lactic acid) (PLA) microspheres prepared by either a solvent-evaporation or a solvent-extraction double-emulsion technique. Particle uptake into intestinal Fever's patches, induction of antibodies in sera and secretion of immunoglobulins by isolated Peyer's patches, lungs and spleen lymphocytes were investigated. Our results revealed size and surface characteristic-dependent uptake of microspheres into Peyer's patches. Microsphere translocation 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 immunization with 0.8-mu m PLG solvent-evaporation microspheres. The immunomodulation was statistically significant as compared to free LW 50020. In contrast, oral immunization with other preparations caused reduced or absent modulation of the immune response compared to 0.8-mu m microspheres and free antigen. These findings indicate that microspheres displaying small particle sizes, rapid antigen release and high antigen content provide optimal tools to deliver orally applied antigens.