Induction of antigen-specific cytotoxic T lymphocytes by immunization with negatively charged soluble antigen through scavenger receptor-mediated delivery

Antigen-specific cytotoxic T lymphocytes (CTL) are essential for the immunotherapy against cancer or infection diseases although, conventionally, immunization with antigens in soluble form cannot induce CTL. In the present study, we have demonstrated for the first time that ovalbumin (OVA)-specific CTL can be induced without any adjuvants by immunization with soluble OVA with negative charges through scavenger-mediated delivery of antigens to antigen presenting cells (APC). Succinylated, maleylated and aconitylated derivatives were synthesized to allow the introduction of negative charges. All these derivatives can induce OVA-specific CTL and, especially, the CTL activity of mice immunized with maleylated derivatives was comparable with that with OVA emulsified with CFA, known to be the strongest adjuvant. Efficient antigen-specific T cell proliferation and IFN-γ production were also observed for the OVA derivatives. The OVA derivatives also showed significant protective effects on the growth of OVA-expressing E.G7 tumor cells. In conclusion, the present study demonstrates that the introduction of negative charges to soluble antigens will be a useful strategy for the development of vaccines.