Fusogenic liposomes efficiently deliver exogenous antigen through the cytoplasm into the MHC class I processing pathway.
Exogenous soluble proteins enter the endosomal pathway by endocytosis and are presented in association with MHC class II rather than class I. In contrast, the delivery of exogenous protein antigens (Ag) into the cytosol generates MHC class I-restricted cytotoxic T lymphocytes (CTL) responses. Although several immunization approaches, such as the utilization of liposomes, have induced the in vivo priming of MHC class I-restricted CTL responses to protein Ag, it remains unclear whether this priming results from the direct delivery of protein Ag to the cytosol. Here we report that fusogenic liposomes (FL), which are prepared by fusing simple liposomes with Sendai virus particles, can deliver the encapsulated soluble protein directly into the cytosol of cells cultured concurrently and introduce it into the conventional MHC class I Ag presentation pathway. Moreover, a single immunization with ovalbumin (OVA) encapsulated in FL but not in simple liposomes results in the potent priming of OVA-specific CTL. Thus, FL function as an efficient tool for the delivery of CTL vaccines.
Nakanishi
T
T
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Hayashi
A
A
Kunisawa
J
J
Tsutsumi
Y
Y
Tanaka
K
K
Yashiro-Ohtani
Y
Y
Nakanishi
M
M
Fujiwara
H
H
Hamaoka
T
T
Mayumi
T
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology; D004337:Drug Carriers; D004705:Endocytosis / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008081:Liposomes; D008561:Membrane Fusion / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000941:Antigens; D004337:Drug Carriers; D015395:Histocompatibility Antigens Class I; D008081:Liposomes; D010047:Ovalbumin