Adjuvancy enhancement of muramyl dipeptide by modulating its release from a physicochemically modified matrix of ovalbumin microspheres: II. In vivo investigation

Abstract

In the present study, sustaining the release of adjuvants was investigated using microspheres as a means to increase the immune response (i.e. efficacy) and, ultimately, to reduce adverse effects to vaccine components. To date, most attempts have focused on sustaining the release of antigens. The utility of currently used vaccine adjuvants may be improved by sustaining their release. The development, modification and characterization of a two-component microsphere vaccine delivery system was demonstrated in our previous report [Puri et al., J. Control. Release (2000) in press]. Briefly, ovalbumin (OVA) was utilized as the model antigen (Ag) and delivery matrix and MDP or threonyl-MDP served as the model adjuvants. The release pattern of MDP was modulated from a physicochemically modified matrix of OVA microspheres (OVA-MSs). The purpose of the present study was to evaluate the adjuvancy of MDP in mice by modulating its release from OVA-MSs. Mice were immunized intradermally (i.d.) with various preparations of OVA-MSs, using a single-shot-immunization technique. Positive and negative control preparations were evaluated as well. An inverse relationship was observed between the in vitro release rate of MDP and the in vivo OVA-specific IgG antibody (Ab) immune response in mice. These results demonstrated that modulating the release pattern of MDP or threonyl-MDP enhanced their adjuvant effect. In conclusion, the current results demonstrate that the sustained and controlled release of adjuvants is extremely important for inducing a high level and prolonged period of immunostimulation while potentially minimizing therapy-limiting adverse effects.