Liposome Formulations of Hydrophobic Drugs

Abstract

Here, we report methods of preparation of liposome vaccine formulations for the entrapment of antigenic peptides and antigen encoding plasmid DNAs. Two examples of liposomal vaccine formulations producing highly effective immune responses are given. Firstly, a formulation with encapsulated antigenic peptides derived from the hepatitis C virus NS4 and the core proteins, and secondly, the encapsulation of a plasmid DNA encoding the gp33 glycoprotein of the lymphocytic choriomeningitis virus (LCMV). Vaccination with liposomal HCV peptides in HLA-A2 transgenic mice by subcutaneous injections induced strong cytotoxic T cell responses as shown by lysis of human target cells expressing HCV proteins. The immunogenicity of the liposomal peptide vaccines was further enhanced by incorporation of immunostimulatory CpG oligonucleotide sequences, shown by a strong increase of the frequency of IFN-gamma secreting cells that persisted at high levels for long periods of time. With the LCMV model, we could show that upon intradermal injection, plasmid-DNA liposomes formed LCMV gp33 antigen depots facilitating long-lasting in vivo antigen loading of dendritic cells (DC), followed by a strong immune response. Our data show that liposomal formulations of peptide or plasmid-DNA vaccines are highly effective at direct in vivo antigen loading and activation of DC leading to protective antiviral and anti-tumor immune responses. 163Chapter 11

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