Liposome-Encapsulated Adjuvants are Potent Inducers of Antigen- Specific T-Cells in Vivo

Abstract

As shown previously, encapsulation of a peptide derived from tyrosinase-related protein2 (TRP2) into liposomes (artificial virus envelope (AVE) 3) resulted in combination with CpG-oligodeoxynucleotides in the induction of higher numbers of antigen-specific T cells compared to vaccination with free TRP2. Here, we present further data with regard to optimal antigen dose, the relevance of vaccine injection site and on the T cell stimulatory synergism of liposomal adjuvant combinations. Compared to an aqueous solution liposomal TRP2 was more potent in the induction of TRP2-specific T cells at an optimal dose but showed a narrow dose optimum with profoundly impaired T cell responses at higher vaccine doses. Higher T cell numbers were induced when mice were vaccinated into their hint foodpads compared to intradermal vaccination, the site used routinely in murine tumor vaccination models. A synergistic adjuvant effect was observed when CpG-oligodeoxynucleotides were admixed with liposomal monophosphoryl lipid A (MPLA) and the lipopeptide Pam3Cys, respectively. In summary our data demonstrate that liposomes as carriers for peptide-antigen and adjuvant induce a strong antigen-specific T cell response and are superior over vaccine formulations composed of free peptide and adjuvant.