Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction.
Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction.
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猪 IgG1 Fc 的表面展示通过促进病毒补体逃逸和哺乳动物细胞转导来增强杆状病毒载体疫苗的功效
DOI：
10.1186/s13567-017-0434-5
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发表时间：
2017-05-12
影响因子：
4.4
通讯作者：
Du E
中科院分区：
文献类型：
--
作者：
Liu Z;Liu Y;Zhang Y;Yang Y;Ren J;Zhang X;Du E
杆状病毒介导的基因转移已被开发为针对许多疾病的疫苗设计策略，而没有明显的病毒复制。然而，它受到补体依赖性失活的阻碍，从而阻碍了杆状病毒的体内应用。已经开发了多种方法来绕过血清中的补体系统。在本研究中，我们构建并筛选了一系列展示补体干扰因子的杆状病毒载体，其中展示猪IgG 1 Fc（pFc）的杆状病毒载体显示最高的补体拮抗作用（75.6%）。流式细胞仪分析表明，杆状病毒展示的pFc的转导效率和报告基因的转基因表达显着增加。在此基础上，构建了表达猪瘟病毒（classical swine fever virus，CSFV）E2基因的杆状病毒表达载体，并构建了假型化表达载体。掺入翻译增强子Syn 21和P10 UTR以提高抗原表达。E2基因在昆虫和哺乳动物细胞中均得到高效表达。用重组杆状病毒免疫猪，产生了高水平的E2特异性抗体、CSFV特异性中和抗体和IFN-γ分泌细胞免疫应答。这些结果表明，表面展示猪IgG 1 Fc的策略具有很大的潜力，以提高杆状病毒载体疫苗的效力，CSFV和其他猪病原体。本文的在线版本（doi：10.1186/s13567-017-0434-5）包含补充材料，可供授权用户使用。
Baculovirus-mediated gene transfer has been developed as a vaccine design strategy against a number of diseases without apparent viral replication. However, it has been hampered by complement-dependent inactivation, thus hindering the in vivo application of baculovirus. A variety of approaches have been exploited to bypass the complement system in the serum. In this study, we constructed and screened a series of baculovirus vectors displaying complement interfering factors, of which a baculovirus vector displaying swine IgG1 Fc (pFc) showed the highest complement antagonism (75.6%). Flow cytometry analysis of transduced cells demonstrated that the baculovirus display of pFc had a significant increase in transduction efficiency and transgene expression of reporter genes. On this basis, a VSV-G-pseudotyped with swine IgG1 Fc surface displayed baculovirus vector was developed to express the classical swine fever virus (CSFV) E2 gene. The translational enhancers Syn21 and P10UTR were incorporated to improve the antigen expression. The E2 gene was efficiently expressed in both insect and mammalian cells. Pigs immunized with this recombinant baculovirus developed high levels of E2-specific antibody, CSFV-specific neutralizing antibody and IFN-γ-secreting cellular immune responses. These results demonstrate that the strategy of surface-displaying swine IgG1 Fc has a great potential to improve the efficiency of baculovirus-vectored vaccine for CSFV and other swine pathogens. The online version of this article (doi:10.1186/s13567-017-0434-5) contains supplementary material, which is available to authorized users.