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BacMam immunization partially protects pigs against sublethal challenge with African swine fever virus

机译:BacMam免疫可以部分保护猪免受非洲猪瘟病毒的亚致死性攻击

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Lack of vaccines and efficient control measures complicate the control and eradication of African swine fever (ASF). Limitations of conventional inactivated and attenuated virus-based vaccines against African swine fever virus (ASFV) highlight the need to use new technologies to develop efficient and safe vaccines against this virus. With this aim in mind, in this study we have constructed BacMam-sHAPQ, a baculovirus based vector for gene transfer into mammalian cells, expressing a fusion protein comprising three in tandem ASFV antigens: p54, p30 and the extracellular domain of the viral hemagglutinin (secretory hemagglutinin, sHA), under the control of the human cytomegalovirus immediate early promoter (CMVie). Confirming its correct in vitro expression, BacMam-sHAPQ induced specific T-cell responses directly after in vivo immunization. Conversely, no specific antibody responses were detectable prior to ASFV challenge. The protective potential of this recombinant vaccine candidate was tested by a homologous sublethal challenge with ASFV following immunization. Four out of six immunized pigs remained viremia-free after ASFV infection, while the other two pigs showed similar viremic titres to control animals. The protection afforded correlated with the presence of a large number of virus-specific IFNγ-secreting T-cells in blood at 17. days post-infection. In contrast, the specific antibody levels observed after ASFV challenge in sera from BacMam-sHAPQ immunized pigs were indistinguishable from those found in control pigs. These results highlight the importance of the cellular responses in protection against ASFV and point towards BacMam vectors as potential tools for future vaccine development.
机译:缺乏疫苗和有效的控制措施使非洲猪瘟(ASF)的控制和根除变得复杂。针对非洲猪瘟病毒(ASFV)的常规灭活和减毒病毒疫苗的局限性突出表明,需要使用新技术来开发针对这种病毒的高效,安全的疫苗。考虑到这一目标,在本研究中,我们构建了BacMam-sHAPQ,这是一种基于杆状病毒的载体,用于将基因转移到哺乳动物细胞中,表达包含三种串联ASFV抗原的融合蛋白:p54,p30和病毒血凝素的胞外域(分泌性血凝素(sHA),在人巨细胞病毒立即早期启动子(CMVie)的控制下。 BacMam-sHAPQ证实了其正确的体外表达,在体内免疫后直接诱导了特异性T细胞应答。相反,在ASFV攻击之前,没有检测到特异性抗体反应。免疫后,用ASFV进行同源致死性攻击,测试了该重组疫苗候选物的保护潜力。在ASFV感染后,六只免疫猪中有四只保持无病毒血症,而其他两只猪的病毒滴度与对照动物相似。感染后17天,血液中存在大量分泌病毒特异性IFNγ的T细胞,这与保护作用有关。相反,BSFMam-sHAPQ免疫猪血清中ASFV攻击后观察到的特异性抗体水平与对照猪中的抗体水平没有区别。这些结果突出了细胞应答在针对ASFV的保护中的重要性,并指出BacMam载体是未来疫苗开发的潜在工具。

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