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) polymers using a solvent evaporation process. The immunoreactivity of the 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 encapsulated Various combinations of small and large microparticles with controlled release characteristics were investigated in CD1 mice. Groups of animals were immunized with 30 mu g equivalent of HBsAg in microparticles per animal. The control group received three injections of 10 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 antibody response at a level comparable to the three-injection alum schedule for at least I year. An in vitro inhibition assay was developed to demonstrate that antigen-antibody reactivity were comparable for the microparticle immunized mice and the alum immunized mice. A competition assay with a monoclonal antibody specific for the neutralizing epitope of HBsAg demonstrated comparable binding for the sera from the microparticle and alum immunized mice. (C) 1997 Elsevier Science Ltd.