APPLICATION OF LIPOSOMES FOR DEVELOPMENT OF ORAL VACCINES - STUDY OF IN-VITRO STABILITY OF LIPOSOMES AND ANTIBODY-RESPONSE TO ANTIGEN ASSOCIATED WITH LIPOSOMES AFTER ORAL IMMUNIZATION

In order to evaluate the usefulness of liposomes as oral vaccines, the stability of liposomes and serum IgA antibody response to antigen ass ociated with liposomes after oral administration were examined. Liposo mes composed of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphos phatidylserine (DPPS), and cholesterol (Chol) (1:1:2, molar ratio), di stearoylphosphatidylcholine (DSPC) and Chol (7:2, molar ratio), and DS PC, DPPS, and Chol (7:3:2 or 1:1:2, molar ratio) were stable in acidic solution (pH 2.0), bile, and pancreatin solution, whereas liposomes c omposed of DPPC and Chol (7:2, molar ratio) and DPPC, DPPS, and Chol ( 7:3:2, molar ratio) were unstable in pH 2.0 and/or bile solutions. Aft er the oral immunization of antigen (ganglioside GM1)-containing lipos omes composed of DPPC, DPPS, and Chol (1:1:2, molar ratio) to mice, th e serum IgA antibody responses against ganglioside GM1 were found. Fur thermore, when monophosphoryl lipid A was incorporated into liposomes containing ganglioside GM1, further augmentation of IgA responses to g anglioside GM1 was observed. On the other hand, the oral administratio n with liposomes composed of DPPC, Chol, and ganglioside GM1 (unstable liposomes), ganglioside GM1 mixed with liposomes composed of DPPC, DP PS and Chol, and ganglioside GM1 alone was unable to induce any detect able anti-ganglioside GM1 IgA antibody responses. These results sugges t that liposomes which showed the stability to acidic solution, bile, and pancreatin solution would serve effectively as an oral delivery ve hicle for inducing mucosal immune responses.