CONTROLLED-RELEASE MICROPARTICLES AS A SINGLE-DOSE HEPATITIS-B VACCINE - EVALUATION OF IMMUNOGENICITY IN MICE

Hepatitis B surface antigen (HBsAg) was encapsulated in microparticles prepared from polylactide-co-glycolide (PLG) and polylactide (PLA) po lymers using a solvent evaporation process. The immunoreactivity of th e entrapped antigen was investigated by SDS-PAGE and Western blot, The microencapsulation process was modified to obtain both small (<10 mu m) and large microparticles (10-100< mu m), 80% of the antigen was enc apsulated Various combinations of small and large microparticles with controlled release characteristics were investigated in CD1 mice. Grou ps of animals were immunized with 30 mu g equivalent of HBsAg in micro particles per animal. The control group received three injections of 1 0 mu g of HBsAg on alum at 0, I and 6 months. Results indicated that a single injection of HBsAg in microparticles could maintain the antibo dy response at a level comparable to the three-injection alum schedule for at least I year. An in vitro inhibition assay was developed to de monstrate that antigen-antibody reactivity were comparable for the mic roparticle immunized mice and the alum immunized mice. A competition a ssay with a monoclonal antibody specific for the neutralizing epitope of HBsAg demonstrated comparable binding for the sera from the micropa rticle and alum immunized mice. (C) 1997 Elsevier Science Ltd.