Immunogenicity of adenovirus vaccines expressing the PCV2 capsid protein in pigs

Immunogenicity of adenovirus vaccines expressing the PCV2 capsid protein in pigs
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猪体内表达 PCV2 衣壳蛋白的腺病毒疫苗的免疫原性

DOI:
10.1016/j.vaccine.2017.07.031
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发表时间:
2017-08-24
期刊:
影响因子:
5.5
通讯作者:
Tong, Dewen
Tong, Dewen
中科院分区:
医学3区
文献类型:
--
作者:
Li, Delong;Du, Qian;Tong, Dewen

文献摘要

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猪圆环病毒2型(PCV2)是猪圆环病毒相关病(PCVAD)的主要病原,给养猪业造成了巨大的经济损失。在前期的研究中,我们构建了表达PCV2 Cap的腺病毒载体疫苗,无论是内含子A和WPRE修饰的,还是CD4OL和GMCSF修饰的,并在小鼠和猪中评估了所有这些疫苗。Ad-A-C-W和Ad-CD40L-Cap-GMCSF的免疫效果虽强于Ad-Cap,但均不及商品化灭活疫苗PCV 2 SH-株。本研究构建了分泌型重组腺病毒Ad-A-spCap-W和Ad-AspCD40L-spCap-spGMCSF-W及非分泌型重组腺病毒Ad-A-CD40L-Cap-GMCSF-W,并通过western blot和激光共聚焦显微镜进行鉴定。ELISA和VN检测结果表明,Ad-A-spCap-W和Ad-A-CD40L-Cap-GMCSF-W诱导的体液免疫应答与SH-株无显著差异,但Ad-A-spCD40L-spCap-spGMCSF-W诱导的体液免疫应答显著高于SH-株。Ad-A-spCap-W和Ad-A-CD40L-Cap-GMCSF-W的淋巴细胞增殖和细胞因子释放水平与SH-株无显著差异,但Ad-A-spCD40L-spCap-spGMCSF-W的淋巴细胞增殖和细胞因子释放水平显著高于SH-株。PCV2攻毒实验表明,Ad-A-spCD40L-spCap-spGMCSF-W免疫组病毒载量明显降低,而Ad-A-spCD40L-spCap-spGMCSF-W免疫组未观察到明显的临床和显微病变。结果表明,重组腺病毒疫苗Ad-A-spCD40L-spCap-spGMCSF-W较市售灭活疫苗PCV2 SH-株具有更强的免疫应答和更好的保护作用,有望成为PCVAD的候选疫苗。(C)2017爱思唯尔有限公司版权所有
Porcine circovirus type 2 (PCV2) is the main pathogen of porcine circovirus associated disease (PCVAD), causing great economic losses in pig industry. In previous study, we constructed adenovirus vector vaccines expressing PCV2 Cap either modified with Intron A and WPRE, or CD4OL and GMCSF, and evaluated all of these vaccines in mice and in pigs. Although Ad-A-C-W and Ad-CD40L-Cap-GMCSF could induce stronger immune responses than Ad-Cap, neither of them was better than commercial inactivated vaccine PCV2 SH-strain. In this study, secretory recombinant adenoviruses (Ad-A-spCap-W and Ad-AspCD40L-spCap-spGMCSF-W) and non-secretory recombinant adenovirus Ad-A-CD40L-Cap-GMCSF-W were constructed, and identified by western blot and confocal laser microscope observation. The results of ELISA and VN showed that humoral immune responses induced by Ad-A-spCap-W and Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH-strain, but Ad-A-spCD40L-spCap-spGMCSF-W could induce significantly higher humoral immune response than SH-strain. Lymphocytes proliferative and cytokines releasing levels of Ad-A-spCap-W and Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH-strain, but Ad-A-spCD40L-spCap-spGMCSF-W was significantly higher than SH-strain. PCV2-challenge experiment showed that virus loads were significantly reduced in Ad-AspCD40L-spCap-spGMCSF-W vaccinated group, and no obviously clinical and microscopic lesions were observed in Ad-A-spCD40L-spCap-spGMCSF-W vaccinated group. Altogether, these results demonstrate that recombinant adenovirus vaccine Ad-A-spCD40L-spCap-spGMCSF-W induces stronger immune responses and provides better protection than commercial inactivated vaccine PCV2 SH-strain, and suggest that Ad-A-spCD40L-spCap-spGMCSF-W could be a potential vaccine candidate against PCVAD. (C) 2017 Elsevier Ltd. All rights reserved.