title: Role of amphotericin B upon enhancement of protective immunity elicited by oral administration with liposome-encapsulated-Japanese encephalitis virus nonstructural protein 1 (NS1) in mice.
abstract: Amphotericin B (AmB) is an antifungal antibiotic the activity of which has been associated with modulation of pro-inflammatory cytokines expression in cultured cells. Herein we reveal that co-administration with AmB enhances the immunogenicity of oral Lip-JENS1 vaccine which derived from liposomes functionalized with DSPC (distearoylphosphatidylcholine) and cholesterol (2:1, molar ratio)-bearing JE virus NS1 protein (600 microg ml(-1)). Oral single dose of Lip-JENS1 elicited a detectable serum NS1-specific IgG antibody response from a mouse model. Remarkably, the addition of AmB (125 microg per mouse), particularly, 2 h prior to, but not simultaneously with, the administration of Lip-JENS1 significantly enhanced the systemic antigen-specific antibody response, providing superior protection against lethal JEV challenges. Further, we observed AmB-induced the transcription of cytokine expression and translocation of transcriptional factor NF-kappaB from the cytoplasm to the nucleus for the murine macrophage J774A.1. Moreover, Peyer's-patch lymphocytes (PPL) from AmB-treated mice produced high levels of IL-1beta, IL-6 and TNF-alpha expression compared to the corresponding control of cells from non-treated mice. Taken together, the results suggest that AmB exerts a profound influence upon mucosal vaccination with Lip-JENS1, possibly playing an adjuvant-augmented role to "fine-tune" humoral as well as cellular immune response, thus conferring enhanced protective immunity for immunising individuals against JE infection.
authors.affiliation: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tsung-Shun
authors.initials: TS
authors.lastname: Lin
authors.forename: Chuan-Chang
authors.initials: CC
authors.lastname: Chuang
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Hsu
authors.forename: Yu-Tien
authors.initials: YT
authors.lastname: Liu
authors.forename: Wen-Po
authors.initials: WP
authors.lastname: Lin
authors.forename: Chung-Chih
authors.initials: CC
authors.lastname: Liang
authors.forename: Wen-Tssann
authors.initials: WT
authors.lastname: Liu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002467:Cell Nucleus / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D004672:Encephalitis, Japanese / Q000517:prevention & control; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008081:Liposomes / Q000008:administration & dosage*; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010581:Peyer's Patches / Q000276:immunology; D016019:Survival Analysis; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D022321:Japanese Encephalitis Vaccines; D008081:Liposomes; D016328:NF-kappa B; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins; D000666:Amphotericin B