State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 43007, China.
Vaccine. 2013 Jun 10;31(26):2796-803. doi: 10.1016/j.vaccine.2013.04.028. Epub 2013 Apr 23.
WH1fungin, a surfactin lipopeptide from Bacillus amyloliquefaciens WH1, can be used as an adjuvant for eliciting strong immune response by parenteral immunization. In this study, WH1fungin was firstly reported as an oral immunoadjuvant. In mice, WH1fungin markedly enhanced the immune response to co-administered protein antigens (OVA or GST), similar to levels elicited by CTB, but no immune response was elicited to itself. Both IgG1 and IgG2a antibodies elicited from the immunizations indicating a mixed Th1/Th2 response. Splenocytes from mice 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. These results further suggested that WH1fungin helps to elicit both humoral and cellular responses to OVA. More studies revealed that the potential mechanism as oral immunoadjuvant was that WH1fungin could form co-precipitates with antigens in a pH value similar to gastric juice. The precipitation protected the antigens from degradation by pepsin providing an explanation for the antigens to withstand the acidic and proteolytic environments of the gastrointestinal tract when co-administered with WH1fungin. Moreover, WH1fungin promoted the uptake of OVA by the intestine and by cultured DC2.4 cells, and increased the expression of cell surface markers and cytokines in DC2.4 cells. Taken together, WH1fungin is a potent oral immunoadjuvant with the ability of protecting protein antigens from acidic and proteolytic degradation, suggesting its potential usage in oral vaccine development.
由解淀粉芽孢杆菌 WH1 产生的 WH1 抗菌肽是一种表面活性的脂肽，可以作为佐剂通过注射免疫来引发强烈的免疫反应。在本研究中，WH1 抗菌肽首次被报道为一种口服免疫佐剂。在小鼠中，WH1 抗菌肽显著增强了与共给药的蛋白抗原（OVA 或 GST）的免疫反应，与 CTB 引发的水平相似，但对自身没有免疫反应。从免疫接种中引发的 IgG1 和 IgG2a 抗体表明存在混合的 Th1/Th2 反应。用 OVA 加 WH1 抗菌肽免疫的小鼠的脾细胞对 OVA CTL 肽刺激产生反应，导致 CD8(+)TNF-α(+)和 CD8(+)IFN-γ(+)T 细胞群增加。这些结果进一步表明，WH1 抗菌肽有助于引发针对 OVA 的体液和细胞反应。进一步的研究表明，作为口服免疫佐剂的潜在机制是 WH1 抗菌肽可以在类似于胃液的 pH 值下与抗原形成共沉淀。沉淀保护抗原免受胃蛋白酶的降解，从而解释了当与 WH1 抗菌肽共同给药时抗原能够耐受胃肠道的酸性和蛋白水解环境。此外，WH1 抗菌肽促进了 OVA 在肠道和培养的 DC2.4 细胞中的摄取，并增加了 DC2.4 细胞表面标志物和细胞因子的表达。总之，WH1 抗菌肽是一种有效的口服免疫佐剂，具有保护蛋白抗原免受酸性和蛋白水解降解的能力，这表明其在口服疫苗开发中的潜在用途。
