Effectiveness of liposomes as potential carriers of vaccines: applications to cholera toxin and human malaria sporozoite antigen.

Abstract

Two antigens, cholera toxin (CT) and a synthetic albumin-conjugated 16-residue peptide derived from the circumsporozoite (CS) protein of Plasmodium falciparum sporozoites, were tested as immunogens in rabbits. The malaria peptide-albumin conjugate by itself was completely nonimmunogenic, and although cholera toxin was immunogenic it also expressed considerable native toxicity. After attachment of CT to liposomes containing ganglioside GM1, toxicity of CT was completely eliminated and antigenicity was enhanced. Therefore liposomes may be capable of reducing toxicity of certain potentially dangerous antigens such as toxins. After incorporation of the malaria peptide-albumin conjugate into liposomes a high titre of specific antibodies was induced against the malaria peptide but not against albumin. These antibodies also reacted with native CS protein. Three adjuvants, including lipid A and two types of lipophilic muramyl dipeptide, were compared and found to be effective in liposomes. Based on the conversion of synthetic P. falciparum CS peptide from a nonimmunogenic to an immunogenic form and on the 'toxoiding' effect of liposomes for CT, it is concluded that liposomes should be considered as being a useful carrier for antigens and adjuvants for vaccines for poorly antigenic or toxic substances.