Muramyl Dipeptide Analogues Of The Biological Activity Screening Of Hepatitis B Surface Antigen Adjuvant Study

China is one of the highly endemic regions in the world for hepatitis B diease. More than 100 million people are carriers of hepatitis B virus among which 30 million people have become patient of chronic hepatitis B. Up to now there is no effective therapy, therefore vaccination becomes of critical importance to control the prevalence of hepatitis B. Aluminium salts have been approved as the adjuvants of hepatitis B vaccine. A lot of research shows that the adjuvants are able to enhance the humoral immune responses and Th2 cellular immune responses. The cellular immune responses is play a critical role in viral clearance during hepatitis B virus infection.Muramyl dipeptide(MDP) was identified in 1974 by Lederer E as the minimum effective component of complete Freud's adjuvant(CFA), a cell wall component of the killed mycobacteria in the preparation. MDP have pleiotropic stimulatory effects on host immune systems and to elicit defensive responses. However, MDP showed significant concomitant side effects in vivo, such as pyrogenicity, and rapid elimination. To improved its pharmacological properties and decreased its side effects, Several hundred derivatives and analogs of MDP have been synthesized through chemically modified and their immunomodulating properties and structure-activity relationships studied. Several compounds have been reported to show strong host-stimulating activities with apyrogenicity. In the present study, we screened sixty MDP analogs through ELISPOT assay, which have been synthesized by Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Materia Medica. We also profoundly studied the immunogenicity of two MDP analogs(5#, 17# compound) through screened, which as adjuvant of HBsAg.Firstly, to study the kinetics of cellular immune responses induced by recombinant HBsAg, 3ug of HBsAg was used to immunize BALB/c mice. The level of IFN-γ expression by splenocytes with HBsAg MHC I peptide S_28-39 in vitro was detected by ELISPOT assay. The results showed that on day 4 postimmunization, the lower cellular immune responses were detected. On day 7 postimmunization, we...