Immunogenicity and lower dose requirement of polymer entrapped tetanus toxoid co-administered with alum

Low adjuvanticity of microparticles based vaccine formulation necessitates the use of alum along with particles to elicit improved antibody titers from single point immunization. It was observed that antibody response from immunization with admixture of alum and polymer entrapped antigen was dependent on particle size, amount of antigen released during burst phase and dose of microencapsulated antigen. In the animals immunized with polymer entrapped tetanus toxoid (TT) very large particles (50-150 microm) did not elicited high antibody titers where as microparticles in the range 2-8 microm exhibited remarkable improvement in the antibody response. Very small size particles (<2 microm) were also not as effective as 2-8 microm size particles for generation of antibody response. Presence of alum improved the immune response by adsorbing the burst released antigen from the particle surfaces. Role of alum in potentiation of immune response from polymer entrapped TT was highly significant at lower dose regimes. Polymer entrapped TT as little as 0.1 Lf when immunized along with alum generated antibody responses superior to those elicited by 10 Lf soluble antigen. Immunization with admixture of particles and alum generated two to three times higher antibody titer than that observed from immunization with similar single doses of alum adsorbed TT. Single point immunization of admixture of particles entrapped TT and alum generated sustained long lasting antibody responses comparable to two divided doses of alum-adsorbed antigen. Superiority of single dose polymeric formulation in comparison to two divided doses of alum adsorbed TT was more evident at lower doses of TT immunization. This reflected the profound synergistic effect of both the adjuvants at lower doses. Affinity of antibodies generated from single point immunization was comparable to that achieved with two doses of alum adsorbed TT immunization. Particle alone elicited more of IgG2a type antibody where as immunization with admixture of alum and particles improved the overall antibody response and more of Th2 type response.