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WH1 真菌来源的表面活性素环肽作为新型佐剂用于肌肉和皮下免疫小鼠。

A surfactin cyclopeptide of WH1fungin used as a novel adjuvant for intramuscular and subcutaneous immunization in mice.

机构信息

Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.

出版信息

Peptides. 2012 Nov;38(1):163-71. doi: 10.1016/j.peptides.2012.08.021. Epub 2012 Sep 12.

DOI:10.1016/j.peptides.2012.08.021
PMID:22982610
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.

摘要

WH1 菌素,一种来自解淀粉芽孢杆菌 WH1 的表面活性素环肽,首先被报道为一种新型免疫佐剂,当与抗原混合使用时,可以显著增强免疫反应。在肌肉内或皮下免疫后,WH1 菌素可以帮助诱导持久的体液和细胞免疫反应,甚至与弗氏佐剂相当。免疫 OVA 加 WH1 菌素的小鼠产生了针对 OVA CTL 肽的 IgG1 和 IgG2a 抗原特异性抗体,表明存在混合的 Th1/Th2 反应。从肌肉内免疫 OVA 加 WH1 菌素的小鼠的脾细胞对 OVA CTL 肽刺激产生反应,导致 CD8+TNF-α+和 CD8+IFN-γ+T 细胞群体增加,而从皮下免疫 OVA 加 WH1 菌素的小鼠的脾细胞对 OVA Th 肽刺激产生反应时,还发现 CD4+TNF-α+和 CD4+IFN-γ+T 细胞群体增加。这些结果进一步表明,WH1 菌素有助于诱导对 OVA 的体液和细胞反应。研究了 WH1 菌素作为免疫佐剂的潜在机制。体外试验表明,WH1 菌素可以进入 RAW 264.7 细胞,诱导 ROS 积累,并增加细胞表面标志物和细胞因子的表达。进一步的研究表明,WH1 菌素可能通过与抗原呈递细胞(如 RAW 264.7)中的 TLR-2 结合发挥其佐剂活性。总之,WH1 菌素作为一种新型佐剂,在未来疫苗的开发中具有很大的潜力。

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