Liposomes as vehicles for vaccines

Abstract

Lipid A from Shigella flexneri LPS, or acylated derivatives of muramyl dipeptide (MDP), were incorporated into the lipid bilayer of liposomes to enhance the adjuvanticity of the liposomes in rabbits. Liposomes containing lipid A induced antibodies against lipid A, phosphocholine, phosphatidylcholine, and sphingomyelin. Lipid A was resolved into eight fractions, some of which did, and others of which did not, induce antibodies against liposomes. Anti-liposome antibodies also were induced (in the absence of liposomes) by complete Freund's adjuvant, and by acid treated bacterial cells coated with lipid A, but were not induced either by lipid A or liposomes alone, or by liposomes containing acylated MDP. We tested the liposomes for the ability to enhance the immunogenicity of a protein antigen. The antigen consisted of liposomes having acylated MDP and ganglioside GM1 (the receptor for cholera toxin, or CT) in the lipid membrane, and CT bound to the outer surface of the liposomes. The liposomal antigen (having surface-bound CT) produced a much greater anti-CT titer than that obtained by injection of CT alone. We conclude that liposomes containing only phosphatidylcholine, cholesterol, and dicetyl phosphate are poorly immunogenic, but that antibodies against them can be induced by inclusion of lipid A. Liposomes that are appropriately formulated can strongly enhance the immunogenicity of a liposome-bound protein antigen.