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由两种免疫显性非洲猪瘟病毒蛋白与细菌脂蛋白 OprI 融合而成的重组蛋白的抗原性和免疫原性。

Antigenic and immunogenic properties of recombinant proteins consisting of two immunodominant African swine fever virus proteins fused with bacterial lipoprotein OprI.

机构信息

State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, China.

出版信息

Virol J. 2022 Jan 21;19(1):16. doi: 10.1186/s12985-022-01747-9.

Abstract

BACKGROUND

African swine fever (ASF) is a highly fatal swine disease, which threatens the global pig industry. There is no commercially available vaccine against ASF and effective subunit vaccines would represent a real breakthrough.

METHODS

In this study, we expressed and purified two recombinant fusion proteins, OPM (OprI-p30-modified p54) and OPMT (OprI-p30-modified p54-T cell epitope), which combine the bacterial lipoprotein OprI with ASF virus proteins p30 and p54. Purified recombinant p30 and modified p54 expressed alone or fused served as controls. The activation of dendritic cells (DCs) by these proteins was first assessed. Then, humoral and cellular immunity induced by the proteins were evaluated in mice.

RESULTS

Both OPM and OPMT activated DCs with elevated expression of relevant surface molecules and proinflammatory cytokines. Furthermore, OPMT elicited the highest levels of antigen-specific IgG responses, cytokines including interleukin-2, interferon-γ, and tumor necrosis factor-α, and proliferation of lymphocytes. Importantly, the sera from mice vaccinated with OPM or OPMT neutralized more than 86% of ASF virus in vitro.

CONCLUSIONS

Our results suggest that OPMT has good immunostimulatory activities and immunogenicity in mice, and might be an appropriate candidate to elicit immune responses in swine. Our study provides valuable information on further development of a subunit vaccine against ASF.

摘要

背景

非洲猪瘟(ASF)是一种高致命性的猪病,威胁着全球的养猪业。目前尚无针对 ASF 的商业可用疫苗,而有效的亚单位疫苗将是一个真正的突破。

方法

在本研究中,我们表达和纯化了两种重组融合蛋白,OPM(OprI-p30 修饰的 p54)和 OPMT(OprI-p30 修饰的 p54-T 细胞表位),它们将细菌脂蛋白 OprI 与 ASF 病毒蛋白 p30 和 p54 结合在一起。单独表达或融合表达的纯化重组 p30 和修饰的 p54 作为对照。首先评估这些蛋白对树突状细胞(DC)的激活作用。然后,评估这些蛋白在小鼠中诱导的体液和细胞免疫。

结果

OPM 和 OPMT 均能激活 DC,使其表面相关分子和促炎细胞因子的表达水平升高。此外,OPMT 引起了最高水平的抗原特异性 IgG 反应、细胞因子(包括白细胞介素 2、干扰素-γ 和肿瘤坏死因子-α)和淋巴细胞增殖。重要的是,用 OPM 或 OPMT 免疫接种的小鼠血清在体外中和了超过 86%的 ASF 病毒。

结论

我们的研究结果表明,OPMT 在小鼠中具有良好的免疫刺激活性和免疫原性,可能是在猪中引发免疫反应的合适候选物。我们的研究为进一步开发 ASF 的亚单位疫苗提供了有价值的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/894d/8781047/daa0b31daa96/12985_2022_1747_Fig1_HTML.jpg

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