CONTROLLED-RELEASE MICROPARTICLES AS A SINGLE-DOSE DIPHTHERIA TOXOID VACCINE - IMMUNOGENICITY IN SMALL ANIMAL-MODELS

Diphtheria toxoid (DT) was encapsulated in microparticles prepared fro m polylactide-co-glycolide (PLG) polymers using a solvent evaporation technique. Combinations of small and large size microparticles with co ntrolled release characteristics were used to immunize Sprague Dawley rats and the antibody responses were monitored for one year. For compa rison, control groups of rats were immunized at 0, 1 and 2 months with DT adsorbed to alum. The antibody responses generated by the micropar ticles were comparable to the alum immunized control groups from 32 we eks. Microparticles with a single entrapped antigen (DT) induced bette r antibody responses that microparticles with two antigens entrapped s imultaneously (DT+TT). Microparticles prepared from a single polymer w ere less effective for long term antibody induction than a combination of microparticles prepared from three different polymers. A combinati on vaccine consisting of antigen adsorbed to alum and also entrapped i n microparticles gave the best response. In an inhibition assay design ed to determine the relative binding of antisera to the antigen, the s era from the microparticle and the alum immunized animals showed compa rable binding. An intradermal challenge study was performed in rabbits , which showed similar levels for the alum and the microparticle immun ized animals at 4, 12 and 32 weeks after immunization. (C) 1998 Elsevi er Science Ltd. All rights reserved.