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在小鼠中使用共表达日本脑炎病毒包膜蛋白和猪白细胞介素-6蛋白的重组腺病毒增强针对日本脑炎病毒的免疫反应。

Enhanced immune responses against Japanese encephalitis virus using recombinant adenoviruses coexpressing Japanese encephalitis virus envelope and porcine interleukin-6 proteins in mice.

作者信息

Liu Hanyang, Wu Rui, Liu Kai, Yuan Lei, Huang Xiaobo, Wen Yiping, Ma Xiaoping, Yan Qigui, Zhao Qin, Wen Xintian, Cao Sanjie

机构信息

Research Center of Swine Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

Research Center of Swine Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

出版信息

Virus Res. 2016 Aug 15;222:34-40. doi: 10.1016/j.virusres.2016.05.025. Epub 2016 May 25.

Abstract

Japanese encephalitis is a reproductive disorder caused by Japanese encephalitis virus (JEV) in swine. Previous studies have demonstrated that recombinant adenovirus serotype 5 (Ad5) may be a potential vaccine candidate because it can express JEV envelope epitopes and induce immune responses against JEV. Still, it will be necessary to develop an adjuvant that can enhance both humoral and cellular immune responses to the recombinant antigen delivered by non-replicating Ad5. In this study, we investigated the systemic immune responses of BALB/c mice immunized with recombinant adenovirus expressing JEV envelope epitopes in combination with porcine interleukin-6 (rAdE-IL-6).The rAdE-IL-6 immunized group had the highest titers of anti-JEV antibody as detected by an enzyme-linked immunosorbent assay (ELISA), as well as the highest levels of neutralizing antibody (1:75) as detected by a serum neutralization test. Similarly, higher concentrations of interferon-gamma (834.7pg/ml) and interleukin-6 (IL-6) (229.7pg/ml) were detected in the rAdE-IL-6 group using an ELISA assay. These data indicate that immunized BALB/c induce a strong cellular response against rAdE-IL-6. Furthermore, after challenge with the virulent JEV SCYA201201 strain, the rAdE-IL-6 group generated an immune protective response 70% greater than that of the control group, indicating that rAdE-IL-6 induced a protective immune response against JEV challenge in mice. The results from this study demonstrated that IL-6 is a strong adjuvant that can enhance both humoral and cellular immune responses in mice. Furthermore, a recombinant adenovirus coexpressing JEV envelope epitopes and porcine IL-6 protein may be an effective vaccine in animals.

摘要

日本脑炎是由猪日本脑炎病毒(JEV)引起的一种繁殖障碍疾病。先前的研究表明,重组5型腺病毒(Ad5)可能是一种潜在的疫苗候选物,因为它可以表达JEV包膜表位并诱导针对JEV的免疫反应。不过,仍有必要开发一种佐剂,以增强对由非复制型Ad5递送的重组抗原的体液免疫和细胞免疫反应。在本研究中,我们调查了用表达JEV包膜表位的重组腺病毒与猪白细胞介素-6(rAdE-IL-6)联合免疫的BALB/c小鼠的全身免疫反应。通过酶联免疫吸附测定(ELISA)检测,rAdE-IL-6免疫组的抗JEV抗体滴度最高,通过血清中和试验检测的中和抗体水平也最高(1:75)。同样,使用ELISA测定法在rAdE-IL-6组中检测到更高浓度的干扰素-γ(834.7pg/ml)和白细胞介素-6(IL-6)(229.7pg/ml)。这些数据表明,免疫的BALB/c小鼠对rAdE-IL-6产生了强烈的细胞反应。此外,在用强毒JEV SCYA201201株攻击后,rAdE-IL-6组产生的免疫保护反应比对照组高70%,表明rAdE-IL-6在小鼠中诱导了针对JEV攻击的保护性免疫反应。本研究结果表明,IL-6是一种强大的佐剂,可以增强小鼠的体液免疫和细胞免疫反应。此外,共表达JEV包膜表位和猪IL-6蛋白的重组腺病毒可能是一种有效的动物疫苗。

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