Adjuvancy enhancement of muramyl dipeptide by controlling its release from ovalbumin microspheres

摘要

Subunit vaccines, having evolved through the advances in molecular biology and recombinant technologies, offer the advantage of safety, but are weakly immunogenic, and therefore require the use of adjuvants. One promising adjuvant is N-acetylmuramyl - L-alanyl - D-isoglutamine (MDP, for muramyl dipeptide). MDP and its derivatives have been reported to function as immunopotentiators in host defense systems. However, parenterally administered MDP is rapidly excreted in urine, thus necessitating the use of high and frequent doses which are associated with pyrogenicity, uveitis and adjuvant-induced arthritis. The aim of this study is to enhance the adjuvancy of MDP by sustaining and controlling its release from surface and bulk modified ovalbiumin microspheres (OVA-MSs). OVA was selected as the model antigen as well as the polymer in this study. Earlier studies doen in our laboratory showed placebo OVA-MSs to be non-immunogenic. The objectives of this study are 1) to formulate and modify MDP loaded OVA-MSs; 2) to perform mechanistic analysis of the in vitro release of OVA and MDP from the microspheres; 3) to evaluate in vivo immune response of surface and bulk modified OVA-MS formulations in mice.