In vivo antigen loading and activation of dendritic cells via a liposomal peptide vaccine mediates protective antiviral and anti-tumour immunity

Initiation of antiviral and anti-tumour T cell responses is probably achiev ed mainly by dendritic cells (DC) transporting antigen fr om the periphery into organised lymphoid tissues. To develop T cell vaccines it is, therefor e, important to understand the accessibility of the antigen to DC in vivo a nd whether DC are activated by vaccination. Here we have evaluated the immu nogenicity of a liposomal vaccine formulation with antigenic peptides deriv ed from the glycoprotein of the lymphocytic choriomeningitis virus. Liposom e-encapsulated peptides were highly immunogenic a hen administered intrader mally and elicited protective antiviral immunity. After intradermal injecti on, liposomes formed antigen depots which facilitated long-lasting in vivo antigen loading of dendritic cells almost exclusively in the local draining lymph nodes. The immunogenicity of the liposomal peptide vaccine was furth er enhanced by incorporation of immunostimulatory oligonucleotides leading to activation of DC. This optimised liposomal peptide vaccine elicited also anti-tumour immunity and induced CTL responses comparable to adoptively tr ansferred, peptide-presenting DC. Thus, our data show that liposomal formul ations of peptide vaccines are highly effective at direct in vivo antigen l oading and activation of DC leading to protective antiviral and anti-tumour immune responses. (C) 2000 Elsevier Science Ltd. All lights reserved.