Enhancing DNA immunization by targeting ASFV antigens to SLA-II bearing cells
Enhancing DNA immunization by targeting ASFV antigens to SLA-II bearing cells
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DOI：
10.1016/j.vaccine.2011.05.084
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发表时间：
2011-07-26
期刊：
影响因子：
5.5
通讯作者：
Rodriguez, F.
中科院分区：
文献类型：
--
作者：
Argilaguet, J. M.;Perez-Martin, E.;Rodriguez, F.
对DNA疫苗的主要批评之一是它们偶尔赋予的免疫原性差，至少在大型动物中。证实了这一理论，用编码两个非洲猪瘟病毒框内基因的质粒DNA（pCMV-PQ）免疫，未能在猪中诱导可检测的免疫应答，而在小鼠中是成功的。为提高猪免疫应答水平，构建了猪白细胞抗原II（Pleukocyte antigen II，PLEACH）特异性抗体单链可变区片段与病毒基因框内融合的重组质粒pCMV-APCH 1 PQ。我们的研究结果清楚地表明，靶向抗原的抗原专业细胞指数增强免疫反应诱导的猪，虽然DNA疫苗是不能赋予保护免受致命的病毒攻击。实际上，在接受pCMV-APCH 1 PQ质粒的每头猪中观察到病毒血症恶化，这与非中和抗体和抗原特异性SLA II限制性T细胞的存在相关。我们的发现对未来非洲猪瘟病毒和其他猪病原体的疫苗开发的影响进行了讨论。(C)2011爱思唯尔有限公司保留所有权利。
One of the main criticisms to DNA vaccines is the poor immunogenicity that they confer on occasions, at least in large animals. Confirming this theory, immunization with plasmid DNA encoding two African swine fever virus genes in frame (pCMV-PQ), failed in inducing detectable immune responses in pigs, while it was successful in mice. Aiming to improve the immune responses induced in swine, a new plasmid was constructed, encoding the viral genes fused in frame with a single chain variable fragment of an antibody specific for a swine leukocyte antigen II (pCMV-APCH1PQ). Our results clearly demonstrate that targeting antigens to antigen professional cells exponentially enhanced the immune response induced in pigs, albeit that the DNA vaccine was not able to confer protection against lethal viral challenge. Indeed, a viremia exacerbation was observed in each of the pigs that received the pCMV-APCH1PQ plasmid, this correlating with the presence of non-neutralizing antibodies and antigen-specific SLA II-restricted T-cells. The implications of our discoveries for the development of future vaccines against African swine fever virus and other swine pathogens are discussed. (C) 2011 Elsevier Ltd. All rights reserved.