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Efficacy of different DNA and MVA prime-boost vaccination regimens against a Rift Valley fever virus (RVFV) challenge in sheep 12 weeks following vaccination

机译:疫苗接种后12周内不同的DNA和MVA初免-加强疫苗接种方案对裂谷热病毒(RVFV)攻击的功效

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摘要

The aim of this work was to evaluate the immunogenicity and efficacy of DNA and MVA vaccines encoding the RVFV glycoproteins Gn and Gc in an ovine model of RVFV infection. Adult sheep of both sexes were challenged 12 weeks after the last immunization and clinical, virological, biochemical and immunological consequences, were analyzed. Strategies based on immunization with homologous DNA or heterologous DNA/MVA prime-boost were able to induce a rapid in vitro neutralizing antibody response as well as IFNγ production after in vitro virus specific re-stimulation. In these animals we observed reduced viremia levels and less clinical signs when compared with mock-immunized controls. In contrast, sheep inoculated with a homologous MVA prime-boost showed increased viremia correlating with the absence of detectable neutralizing antibody responses, despite of inducing cellular responses after the last immunization. However, faster induction of neutralizing antibodies and IFNγ production after challenge were found in this group when compared to the mock vaccinated group, indicative of a primed immune response. In conclusion, these results suggest that vaccination strategies based on DNA priming were able to mount and maintain specific anti-RVFV glycoprotein immune responses upon homologous or heterologous booster doses, warranting further optimization in large animal models of infection.Electronic supplementary materialThe online version of this article (10.1186/s13567-018-0516-z) contains supplementary material, which is available to authorized users.
机译:这项工作的目的是评估在绵羊RVFV感染模型中编码RVFV糖蛋白Gn和Gc的DNA和MVA疫苗的免疫原性和效力。上次免疫后12周对两成年绵羊进行攻击,并分析其临床,病毒学,生化和免疫学后果。基于同源DNA或异源DNA / MVA初免-加强免疫的策略能够在体外病毒特异性重新刺激后诱导快速的体外中和抗体反应以及IFNγ产生。与模拟免疫对照相比,在这些动物中我们观察到病毒血症水平降低,临床体征减少。相反,尽管在最后一次免疫后诱导了细胞反应,但接种了同源MVA初免-加强病毒的绵羊显示病毒血症增加,且与缺乏可检测的中和抗体反应有关。然而,与模拟疫苗接种组相比,在该组中发现攻击后中和抗体的更快诱导和IFNγ产生,这表明引发了免疫反应。总之,这些结果表明,基于DNA引发的疫苗接种策略能够在同源或异源加强剂量后安装并维持特定的抗RVFV糖蛋白免疫反应,从而保证在大型动物感染模型中进一步优化。文章(10.1186 / s13567-018-0516-z)包含补充材料,授权用户可以使用。

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