Enhanced immune response after subcutaneous and oral immunization with biodegradable PLGA microspheres

PLGA microspheres containing bovine serum albumin (BSA) as a model antigen, were prepared by a double emulsion/solvent extraction method and their in vitro characterization was performed. The same microspheres were used in a series of in vivo studies to evaluate the immune response induced after sub cutaneous or oral inoculation following different immunization protocols. T he in vivo data confirm that the immunogenicity of the albumin is not affec ted by the encapsulation procedure. The subcutaneous administration of micr ospheres showed an immune response (serum IgG levels by ELISA) statisticall y above BSA solution, even when the dose administered was 10 times lower. T he adjuvanticity of the microspheres was found to be comparable to that of Freund's complete adjuvant (FCA), but in contrast to FCA they are biocompat ible and did not induce any adverse reaction at the site of injection. A si ngle oral administration of the microspheres was not a successful strategy for the induction of a reproducible response. Therefore, microspheres of 1 and 5 mu m were orally administered on 3 consecutive days and the response obtained showed that the use of a boosting dose was not necessary for the 1 mu m particles. These results suggest the possibility of simplifying the i mmunization schedule to a primary immunization if 1 mu m particles are admi nistered. (C) 1998 Elsevier Science B.V. All rights reserved.