A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong.
A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong.
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DOI：
10.4269/ajtmh.15-0771
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Lee J
中科院分区：
文献类型：
--
作者：
Choi S;Jeong HJ;Hwang KJ;Gill B;Ju YR;Lee YS;Lee J
我们研究了 47 kDa 外膜蛋白 (OMP)，它是一种周质丝氨酸蛋白酶，也是恙虫病东方体的抗原主要表面蛋白，作为候选疫苗。我们开发了表达重组 47-kDa OMP (rec47) 的传统亚单位疫苗和 DNA 疫苗 (p47)。在小鼠免疫实验中，单独使用rec47或使用rec47加上来自大肠杆菌的不耐热肠毒素B亚基或加上霍乱毒素（CT）作为佐剂的鼻内免疫比仅使用p47或使用p47加上pBOOST2-samIRF7/3（pB）作为佐剂的肌内免疫诱导更高量的rec47特异性抗体。此外，如脾细胞增殖测定所示，rec47 和 CT 的组合诱导了对 47-kDa OMP 的强烈细胞免疫反应，并且如细胞因子酶联免疫吸附测定所示，还诱导了 Th1 和 Th2 型细胞因子的产生。使用rec47加CT进行鼻内免疫是诱导体液和细胞介导的免疫反应的最有效方法。此外，在用rec47加CT免疫的小鼠中观察到针对同源恙虫病菌株Boryong攻击的相对较强的保护作用。因此，47-kDa OMP 是开发针对恙虫病感染引起的恙虫病的预防性疫苗的有吸引力的候选者。
We investigated the 47-kDa outer membrane protein (OMP), which is a periplasmic serine protease and an antigenic major surface protein of Orientia tsutsugamushi, as a vaccine candidate. We developed a conventional subunit vaccine expressing recombinant 47-kDa OMP (rec47) and a DNA vaccine (p47). In mouse immunization experiments, intranasal immunization with rec47 alone or with rec47 plus heat-labile enterotoxin B subunit from Escherichia coli or plus cholera toxin (CT) as adjuvants induced a higher amount of rec47-specific antibodies than intramuscular immunization with p47 alone or with p47 plus pBOOST2-samIRF7/3 (pB) as adjuvant. Moreover, the combination of rec47 and CT induced a strong cellular immune response to 47-kDa OMP, as demonstrated by a spleen cell proliferation assay, and also induced Th1- and Th2-type cytokine production, as demonstrated by a cytokine enzyme-linked immunosorbent assay. Intranasal immunization with rec47 plus CT was the most effective method for the induction of humoral and cell-mediated immune responses. Furthermore, relatively strong protection against homologous O. tsutsugamushi strain Boryong challenge was observed in mice immunized with rec47 plus CT. Therefore, 47-kDa OMP is an attractive candidate for developing a prophylactic vaccine against scrub typhus by O. tsutsugamushi infection.
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