IMMUNOGENICITY AND PROTECTION IN SMALL-ANIMAL MODELS WITH CONTROLLED-RELEASE TETANUS TOXOID MICROPARTICLES AS A SINGLE-DOSE VACCINE

Tetanus toxoid (TT) was encapsulated in microparticles prepared from p olylactide-co-glycolide polymers by a solvent-evaporation technique. C ombinations of small- and large-sized microparticles with controlled-r elease characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, cont rol groups of rats were immunized at 0, 1, and 2 months with TT adsorb ed to alum. The antibody responses generated by the TT entrapped in mi croparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than micropa rticles with two antigens (TT and diphtheria toroid) entrapped simulta neously. A combination vaccine consisting of TT adsorbed to alum and a lso entrapped in microparticles gave the best antibody responses. In a n inhibition assay designed to determine the relative levels of bindin g of antisera to the antigens, the sera from the microparticle- and th e alum-immunized animals showed comparable levels of binding. In addit ion, in a passive-challenge study with mice, TT adsorbed to alum and T T entrapped in microparticles provided equal levels of protection agai nst a lethal challenge with tetanus toxin. An intradermal-challenge st udy was also performed with rabbits, which showed similar levels of pr otection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization.