DEPENDENCE OF RICIN TOXOID VACCINE EFFICACY ON THE STRUCTURE OF POLY(LACTIDE-CO-GLYCOLIDE) MICROPARTICLE CARRIERS

Biodegradable microparticles made of poly(lactide-co-glycolide) (PLG) were used for protracted and pulsed-release of the incorporated ricin toroid (RT) vaccine to reduce the multiple immunization doses and the time required to induce complete protection against lethal aerosol-bor ne ricin challenge. The release rate of RT encapsulated in PLG micropa rticles was controlled by polymer selection and varying the preparatio n procedures, which allowed us to control microparticle size and the d istribution of the vaccine in the polymeric matrix. PLG-microparticles in which RT vaccine was distributed heterogeneously in small pockets stimulated a rapid antibody response which was independent of the poly meric composition of the carriers. PLG-microparticles in which RT vacc ine was distributed homogeneously throughout the polymeric matrix indu ced a slower antibody response, which depended on the polymeric compos ition of the carriers. Administration of RT in homogeneous micropartic les made from 50/50 PLG or 100% polylactide stimulated two distinct an ti-ricin IgG peaks, while RT in heterogeneous microparticles stimulate d identical IgG peaks. An early (3 weeks) and long-lasting (1 year or longer) anti-ricin antibody response was evoked by a single administra tion of encapsulated RT vaccine when prepared by the above-mentioned c onditions. In contrast, three administrations of the aqueous RT were r equired to stimulate similar antibody response. Reduction of immunizat ion time from 6 to 4 weeks was achieved with RT encapsulated in small homogeneous microparticles but not with homogeneous large microparticl es. These results demonstrated the usefulness of biodegradable micropa rticles to improve the efficacy of immunization with RT vaccine and pr obably many other vaccines as well.