Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR^-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR^-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7–10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV.

克里米亚-刚果出血热病毒（CCHFV）是is传播的病毒，能够在人类中引起严重的出血热疾病。当前没有获得许可的疫苗来预防CCHFV相关疾病。我们开发了一种表达CCHFV的M段糖蛋白前体基因的DNA疫苗，并在两种致命的小鼠疾病模型（I型干扰素受体敲除（IFNAR ^-/-）小鼠）中评估了其免疫原性和保护功效。和一种新型的瞬时免疫抑制（IS）小鼠模型。通过对M段DNA疫苗进行肌肉电穿孔对小鼠进行疫苗接种，在两次IFNAR ^-/-接种3次后，均产生具有中和效价的强抗原特异性体液免疫反应^。和IS鼠标模型。为了比较疫苗在两种模型中的保护效果，将经致死剂量的CCHFV毒株IbAr 10200腹膜内（IP）攻击成组的疫苗接种小鼠（每组7-10只）。经CCHFV DNA疫苗接种的体重减轻明显减少小鼠与对照相比。此外，尽管所有载体对照接种的小鼠在第5天都死于疾病，但DNA疫苗可保护超过60％的动物免于致死性疾病。两种模型的小鼠都产生了相当水平的抗体，但IS小鼠对疫苗的Th1 / Th2反应更为均衡。在两种模型中，疫苗的保护功效没有统计学差异。