PROCESS FOR SYNTHESIS OF NOVEL MANNOSE-RECEPTOR SELECTIVE LYSINYLATED CATIONIC AMPHIPHILE FOR INVIVO DELIVERY OF DNA VACCINES

摘要

The present invention discloses processes for preparing a novel series of lysinylated cationic amphiphiles containing both guanidine as well as mannose-mimicking polar shikinoyl and quinoyl head-groups. The findings described herein also demonstrate that compounds of the present invention can target DNA vaccines to antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs), via mannose receptors expressed on the cell surface of APCs. The cationic amphiphiles disclosed herein show enhanced cellular and humoral immune response compared to their mannosyl counterparts in genetic immunization in mice. The present invention discloses that immunization with electrostatic complexes (lipoplexes) of DNA vaccines encoding melanoma antigens (gp100 and tyrosinase) and - liposome of the presently described novel lysinylated cationic amphiphiles with mannose-mimicking shikimoyl headgroups provides long-lasting (100 days post melanoma tumor challenge) protective immunity in all immunized mice. Cationic amphiphiles with mannose-mimicking shikimoyl head-groups described in the present invention are likely to find future applications in the field of genetic immunization.