Sendai virus fusion protein mediates simultaneous induction of MHC class I/II-dependent mucosal and systemic immune responses via the nasopharyngeal-associated lymphoreticular tissue immune system.
Nasal administration of Ags using a novel hybrid Ag delivery vehicle composed of envelope glycoproteins of Sendai virus on the surface of liposome membranes (fusogenic liposome) efficiently delivered Ags to Ag-sampling M cells in nasopharyngeal-associated lymphoreticular tissue. Additionally, fusogenic liposomes also effectively delivered the Ags into epithelial cells and macrophages in nasopharyngeal-associated lymphoreticular tissue and nasal passages. In vitro Ag presentation assays clearly showed that fusogenic liposomes effectively presented encapsulated Ags via the MHC class II-dependent pathway of epithelial cells as well as macrophages. Fusogenic liposomes also have an adjuvant activity against mucosal epithelial cells to enhance MHC class II expression. According to these high delivery and adjuvant activities of fusogenic liposomes, nasal immunization with OVA-encapsulated fusogenic liposomes induced high levels of OVA-specific CD4(+) Th1 and Th2 cell responses. Furthermore, Ag-specific CTL responses and Ab productions were also elicited at both mucosal and systemic sites by nasal immunization with Ag-encapsulated fusogenic liposomes. These results indicate that fusogenic liposome is a versatile and effective system for the stimulation of Ag-specific immune responses at both mucosal and systemic compartments.
Kunisawa
J
J
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Research Institute for Microbial Diseases, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nakanishi
T
T
Takahashi
I
I
Okudaira
A
A
Tsutsumi
Y
Y
Katayama
K
K
Nakagawa
S
S
Kiyono
H
H
Mayumi
T
T
D000281:Administration, Intranasal; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002460:Cell Line; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000502:physiology*; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012157:Mononuclear Phagocyte System / Q000276:immunology* / Q000821:virology; D009297:Nasal Mucosa / Q000276:immunology* / Q000821:virology; D009305:Nasopharynx / Q000276:immunology* / Q000821:virology; D018108:Respirovirus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008081:Liposomes; D014760:Viral Fusion Proteins