title: A surfactin cyclopeptide of WH1fungin used as a novel adjuvant for intramuscular and subcutaneous immunization in mice.
abstract: WH1fungin, a surfactin cyclopeptide from Bacillus amyloliquefaciens WH1, is firstly reported as a novel immunoadjuvant, which can markedly enhance the immune response when given in mixture with antigens. After intramuscular or subcutaneous immunization, WH1fungin can help to induce both of durable humoral and cellular immune response, even as strong as Freund's adjuvant. Both IgG1 and IgG2a antigen-specific antibodies were elicited from the immunizations indicating a mixed Th1/Th2 response. Splenocytes from mice intramuscularly immunized with OVA plus WH1fungin responded to OVA CTL peptide stimulation resulting in an increase in CD8(+)TNF-α(+) and CD8(+)IFN-γ(+) T cell populations, and also an increase in CD4(+)TNF-α(+) T cells and CD4(+)IFN-γ(+) T cell populations was found from mice subcutaneously immunized with OVA plus WH1fungin when responded to OVA Th peptide stimulation. These results further suggest that WH1fungin helps to elicit humoral and cellular responses to OVA. The potential mechanism of WH1fungin as an immunoadjuvant was investigated. In vitro assays showed that WH1fungin could enter into RAW 264.7 cells, induce ROS accumulation, and increase the expression of cell surface markers and cytokines in cells. Further investigation suggested that WH1fungin might exert its adjuvant activity by ligating with TLR-2 in antigen present cells such as RAW 264.7. Taken together, WH1fungin is very potent as a novel adjuvant for development of vaccines in the future.
authors.affiliation: Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Zhenqiu
authors.initials: Z
authors.lastname: Gao
authors.forename: Shengying
authors.initials: S
authors.lastname: Wang
authors.forename: Gaofu
authors.initials: G
authors.lastname: Qi
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D007156:Immunologic Memory / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D055666:Lipopeptides / Q000276:immunology* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D055666:Lipopeptides; D017382:Reactive Oxygen Species; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C555918:WH1fungin; D007371:Interferon-gamma; D010047:Ovalbumin