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针对口蹄疫病毒进行DNA疫苗接种的衣壳前体多肽P1和衣壳蛋白VP1 cDNA载体的比较研究。

Comparative studies of the capsid precursor polypeptide P1 and the capsid protein VP1 cDNA vectors for DNA vaccination against foot-and-mouth disease virus.

作者信息

Yang Ning-Sun, Wang Jeng-Hwan, Lin Ku-Feng, Wang Chien-Yu, Kim Suk-Am, Yang Yu-Ling, Jong Ming-Hwa, Kuo Tsun-Yung, Lai Shiow-Suey, Cheng R Holland, Chan Ming-Tsair, Liang Shu-Mei

机构信息

Institute of BioAgricultural Sciences, Academia Sinica, Taipei, 11529, Taiwan, ROC.

出版信息

J Gene Med. 2005 Jun;7(6):708-17. doi: 10.1002/jgm.723.

Abstract

BACKGROUND

Foot-and-mouth disease virus (FMDV) causes a severe livestock disease, and the virus is an interesting target for virology and vaccine studies.

MATERIALS AND METHODS

Here we evaluated comparatively three different viral antigen-encoding DNA sequences, delivered via two physical means (i.e., gene gun delivery into skin and electroporation delivery into muscle), for naked DNA-mediated vaccination in a mouse system.

RESULTS

Both methods gave similar results, demonstrating commonality of the observed DNA vaccine effects. Immunization with a cDNA vector expressing the major viral antigen (VP1) alone routinely failed to induce the production of anti-VP1 or neutralizing antibodies in test mice. As a second approach, the plasmid L-VP1 that produces a transgenic membrane-anchored VP1 protein elicited a strong antibody response, but all test mice failed in the FMDV challenge experiment. In contrast, for mice immunized with the viral capsid precursor protein (P1) cDNA expression vector, both neutralizing antibodies and 80-100% protection in test mice were detected.

CONCLUSIONS

This strategy of using the whole capsid precursor protein P1 cDNA for vaccination, intentionally without the use of virus-specific protease or other encoding genes for safety reasons, may thus be employed as a relevant experimental system for induction or upgrading of effective neutralizing antibody response, and as a convenient surrogate test system for DNA vaccination studies of FMDV and presumably other viral diseases.

摘要

背景

口蹄疫病毒(FMDV)可引发严重的家畜疾病,该病毒是病毒学和疫苗研究的一个有趣靶点。

材料与方法

在此,我们在小鼠系统中比较评估了通过两种物理方式(即基因枪注射至皮肤和电穿孔注射至肌肉)递送的三种不同的病毒抗原编码DNA序列用于裸DNA介导的疫苗接种的效果。

结果

两种方法产生了相似的结果,表明所观察到的DNA疫苗效果具有共性。单独用表达主要病毒抗原(VP1)的cDNA载体进行免疫通常无法在受试小鼠中诱导产生抗VP1抗体或中和抗体。作为第二种方法,产生转基因膜锚定VP1蛋白的质粒L-VP1引发了强烈的抗体反应,但所有受试小鼠在口蹄疫病毒攻毒实验中均失败。相比之下,对于用病毒衣壳前体蛋白(P1)cDNA表达载体免疫的小鼠,在受试小鼠中检测到了中和抗体以及80%-100%的保护率。

结论

出于安全考虑,故意不使用病毒特异性蛋白酶或其他编码基因,采用全衣壳前体蛋白P1 cDNA进行疫苗接种的这一策略,可作为诱导或提升有效中和抗体反应的相关实验系统,以及口蹄疫病毒及可能其他病毒性疾病DNA疫苗研究的便捷替代测试系统。

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