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基于坏死毒素 N 端结构域的支气管败血波氏杆菌亚单位疫苗的免疫原性和保护效果。

Immunological and protective effects of Bordetella bronchiseptica subunit vaccines based on the recombinant N-terminal domain of dermonecrotic toxin.

机构信息

College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, Shandong, China.

College of Animal Science and Technology, Shandong Agricultural University, Taian 271018, Shandong, China.

出版信息

Int Immunopharmacol. 2015 Oct;28(2):952-9. doi: 10.1016/j.intimp.2015.08.018. Epub 2015 Sep 1.

Abstract

Dermonecrotic toxin (DNT) produced by Bordetella bronchiseptica (B. bronchiseptica) can cause clinical turbinate atrophy in swine and induce dermonecrotic lesions in model mice. We know that the N-terminal of DNT molecule contains the receptor-binding domain, which facilitates binding to the target cells. However, we do not know whether this domain has sufficient immunogenicity to resist B. bronchiseptica damage and thereby to develop a subunit vaccine for the swine industry. In this study, we prokaryotically expressed the recombinant N-terminal of DNT from B. bronchiseptica (named DNT-N) and prepared it for the subunit vaccine to evaluate its immunogenicity. Taishan Pinus massoniana pollen polysaccharide (TPPPS), a known immunomodulator, was used as the adjuvant to examine its immune-conditioning effects. At 49 d after inoculation, 10 mice from each group were challenged with B. bronchiseptica, and another 10 mice were intradermally challenged with native DNT, to examine the protection imparted by the vaccines. The immune parameters (T-lymphocyte counts, cytokine secretions, serum antibody titers, and survival rates) and skin lesions were determined. The results showed that pure DNT-N vaccine significantly induced immune responses and had limited ability to resist the B. bronchiseptica and DNT challenge, whereas the mice administered with TPPPS or Freund's incomplete adjuvant vaccine could induce higher levels of the above immune parameters. Remarkably, the DNT-N vaccine combined with TPPPS adjuvant protected the mice effectively to prevent B. bronchiseptica infection. Our findings indicated that DNT-N has potential for development as an effective subunit vaccine to counteract the damage of B. bronchiseptica infection, especially when used conjointly with TPPPS.

摘要

支气管败血波氏杆菌(Bordetella bronchiseptica)产生的坏死毒素(DNT)可导致猪临床鼻甲萎缩,并在模型小鼠中诱导皮肤坏死病变。我们知道 DNT 分子的 N 端含有受体结合域,有利于与靶细胞结合。然而,我们尚不清楚该结构域是否具有足够的免疫原性,以抵抗博德特氏菌的损伤,从而为养猪业开发亚单位疫苗。在这项研究中,我们原核表达了来自博德特氏菌的 DNT 的重组 N 端(命名为 DNT-N),并将其制备成亚单位疫苗,以评估其免疫原性。泰山马尾松花粉多糖(TPPPS)作为一种已知的免疫调节剂,被用作佐剂,以检验其免疫调节作用。接种后 49 天,每组 10 只小鼠分别用博德特氏菌和天然 DNT 进行皮内攻毒,以检验疫苗的保护作用。测定免疫参数(T 淋巴细胞计数、细胞因子分泌、血清抗体滴度和存活率)和皮肤病变。结果表明,单纯 DNT-N 疫苗能显著诱导免疫应答,抵抗博德特氏菌和 DNT 攻击的能力有限,而给予 TPPPS 或弗氏不完全佐剂的疫苗能诱导更高水平的上述免疫参数。值得注意的是,DNT-N 疫苗联合 TPPPS 佐剂能有效保护小鼠,预防博德特氏菌感染。我们的研究结果表明,DNT-N 具有作为一种有效的亚单位疫苗抵抗博德特氏菌感染的潜力,特别是与 TPPPS 联合使用时。

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