LIPOSOME-IMMUNOSTIMULANT ADJUVANT SYSTEM

THIS PROJECT IS DIRECTED TOWARD DEVELOPMENT AND TESTING OF A LIPOSOMAL ADJUVANT SYSTEM THAT WILL ENGENDER A STRONG AND SUSTAINED IMMUNE RESPONSE TO ANTIGENS OF LOW IMMUNOGENICITY. THIS ADJUVANT SYSTEM WILL CONSIST OF LIPOSOMES THAT CONTAIN ONE OR MORE NONTOXIC IMMUNOPOTENTIATORS OF MICROBIAL OR SYNTHETIC ORIGIN. THESE IMMUNOPOTENTIATORS ARE HIGHLY ACTIVE AS ADJUVANTS WHEN ADMINISTERED IN OIL-IN-WATER EMULSIONS. TWO POSSIBLE MODES OF ANTIGEN INCORPORATION, ENCAPSULATION AND COVALENT ATTACHMENT, WILL BE EVALUATED. THE PERFORMANCE OF LIPOSOMALADJUVANTS WITH POLYSACCHARIDE, PEPTIDE, AND PROTEIN ANTIGENSWILL BE ASSESSED TO ESTABLISH THE GENERAL UTILITY OF THIS APPROACH. SEVERAL IMMUNOLOGICAL CRITERIA WILL BE USED TO EVALUATE THESE LIPOSOMAL VACCINES: (1) THE MAGNITUDE OF THE HUMORAL AND CELL-MEDIATED IMMUNE RESPONSES; (2) THE DISTRIBUTION OF ANTIBODY CLASSES AND IGG SUBCLASSES; AND (3) THE RESPONSE TOSECONDARY IMMUNIZATIONS (IMMUNOLOGICAL MEMORY). THE ABILITYOF THESE LIPOSOMAL VACCINES TO STIMULATE NONSPECIFIC RESISTANCE AGAINST AN ANTIGENICALLY UNRELATED PATHOGEN WILL ALSO BE EVALUATED, USING A MURINE BACTERIAL CHALLENGE MODEL. IT IS ANTICIPATED THAT DATA FROM THESE EXPERIMENTS WILL PROVIDE A FOUNDATION AND A RATIONALE FOR AN EXPANDED PHASE II PROJECT, WHICH WILL INCLUDE CLINICAL TRIALS OF THESE LIPOSOMAL ADJUVANTS IN HUMANS.