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表达犬新孢子虫抗原的家蚕核型多角体病毒作为预防小鼠犬新孢子虫感染的候选疫苗。

Bombyx mori nucleopolyhedrovirus displaying neospora caninum antigens as a vaccine candidate against N. caninum infection in mice.

作者信息

Kato Tatsuya, Otsuki Takahiro, Yoshimoto Mai, Itagaki Kohei, Kohsaka Tetsuya, Matsumoto Yumino, Ike Kazunori, Park Enoch Y

机构信息

Laboratory of Biotechnology, Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan,

出版信息

Mol Biotechnol. 2015 Feb;57(2):145-54. doi: 10.1007/s12033-014-9810-9.

Abstract

Baculovirus display systems have been utilized for cell-specific gene transfer, regenerative medicine, and as vaccine vectors. In particular, baculovirus particles displaying surface antigens have been used as vaccines against some parasites and viruses. In this study, Bombyx mori nucleopolyhedrovirus (BmNPV) particles displaying Neospora caninum antigens (NcSAG1, NcSRS2, and NcMIC3) purified from the hemolymph or fat body of silkworm larvae were prepared to vaccinate mice against N. caninum. Each antigen was expressed on the surface of BmNPV particles through glycoprotein 64 transmembrane and cytoplasmic domains. Antigen-specific antibody production was induced in mice by immunization with each recombinant BmNPV particle. NcMIC3-displaying BmNPV particles purified from the fat body induced a lower antibody titer than particles purified from the hemolymph. Antigen-specific IgG2a was predominantly produced in mice by immunization with NcSAG1-displaying BmNPV particles compared to IgG1, and induction of IFN-γ was dominant, indicating that antigen-displaying BmNPV particles can elicit a Th1 immune response in mice. Semi-quantitative PCR analysis revealed that immunization with each antigen-displaying BmNPV particle partially protected mice from cerebral N. caninum infection. These results suggest that antigen-displaying BmNPV particles can provide an alternative method of controlling neosporosis in cattle and represent a new generation of N. caninum vaccines.

摘要

杆状病毒展示系统已被用于细胞特异性基因转移、再生医学以及作为疫苗载体。特别是,展示表面抗原的杆状病毒颗粒已被用作针对某些寄生虫和病毒的疫苗。在本研究中,制备了从家蚕幼虫血淋巴或脂肪体中纯化的展示犬新孢子虫抗原(NcSAG1、NcSRS2和NcMIC3)的家蚕核型多角体病毒(BmNPV)颗粒,用于给小鼠接种以预防犬新孢子虫感染。每种抗原通过糖蛋白64跨膜和细胞质结构域在BmNPV颗粒表面表达。通过用每种重组BmNPV颗粒免疫,在小鼠中诱导产生了抗原特异性抗体。从脂肪体中纯化的展示NcMIC3的BmNPV颗粒诱导的抗体滴度低于从血淋巴中纯化的颗粒。与IgG1相比,用展示NcSAG1的BmNPV颗粒免疫小鼠主要产生抗原特异性IgG2a,并且IFN-γ的诱导占主导,表明展示抗原的BmNPV颗粒可以在小鼠中引发Th1免疫反应。半定量PCR分析表明,用每种展示抗原的BmNPV颗粒免疫可部分保护小鼠免受脑犬新孢子虫感染。这些结果表明,展示抗原的BmNPV颗粒可以提供一种控制牛新孢子虫病的替代方法,并代表了新一代犬新孢子虫疫苗。

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