Enhanced immunogenicity of the modified GP5 of porcine reproductive and respiratory syndrome virus
Enhanced immunogenicity of the modified GP5 of porcine reproductive and respiratory syndrome virus
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猪繁殖与呼吸综合征病毒GP5修饰增强免疫原性
DOI：
10.1007/s11262-005-5839-y
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发表时间：
2006-02-01
期刊：
影响因子：
1.6
通讯作者：
Chen, HH
中科院分区：
文献类型：
--
作者：
Fang, LR;Jiang, YB;Chen, HH
ORF5编码的主要包膜糖蛋白(GP5)是猪繁殖与呼吸综合征病毒(PRRSV)的关键免疫原蛋白之一，是新一代猪繁殖与呼吸综合征疫苗研制的主要靶点。然而，在几种已开发的表达PRRSV GP5的实验疫苗中已经产生了弱的和迟缓的中和抗体。最近的证据表明，在GP5的中和表位上游存在一个非中和诱饵表位，这可能会阻止对PRRSV产生强大的中和抗体反应。在本研究中，我们对ORF5基因进行了修饰，在中和表位和诱骗表位之间插入了一个PanDR辅助性T细胞表位(PADRE)，以最小化或消除非中和表位的诱骗作用。用DNA疫苗进一步评价了修饰后的GP5的免疫原性。结果表明，与天然的GP5相比，用表达修饰的GP5的DNA构建体免疫的小鼠产生了显著增强的中和抗体。还观察到GP5特异性的ELISA抗体水平和T细胞增殖活性略有增加。这些结果表明，修饰后的GP5具有较高的免疫原性，这可能为今后改进的PRRS疫苗的开发提供便利。
The ORF5-encoded major envelope glycoprotein (GP5) is one of the key immunogenic proteins of the porcine reproductive and respiratory syndrome virus (PRRSV) and is the leading target for the development of the new generation of vaccines against PRRS. However, weak and tardy neutralizing antibodies have been elicited in several developed experimental vaccines expressing PRRSV GP5. More recent evidence has demonstrated a non-neutralizing decoy epitope upstream of the neutralizing epitope of GP5, which might prevent the development of a strong neutralizing antibody response against PRRSV. In the present study, we modified the ORF5 gene by inserting a Pan DR T-helper cell epitope (PADRE) between the neutralizing epitope and the decoy epitope to minimize or eliminate the decoy effect of the non-neutralizing epitope. The immunogenicity of the modified GP5 was further evaluated using DNA vaccination. The results showed that significantly enhanced neutralizing antibodies were elicited in mice immunized with the DNA construct expressing the modified GP5 compared with the native GP5. Slightly increased levels of GP5-specific ELISA antibodies and T-cell proliferative activities were also observed. These results indicate that the high immunogenicity of the modified GP5 might facilitate the development of improved PRRS vaccines in the future.