Tipih Thomas, Heise Mark, Burt Felicity Jane
Division of Virology, University of the Free State, Bloemfontein 9300, South Africa.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Vaccines (Basel). 2021 Dec 16;9(12):1491. doi: 10.3390/vaccines9121491.
Crimean-Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice ( < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.
克里米亚-刚果出血热病毒（CCHFV）极少导致人类出血热，病死率为30%。目前，既没有国际上批准的抗病毒药物，也没有针对该病毒的疫苗。制备了一种基于辛德毕斯病毒载体的复制子，其编码来自南非分离株的CCHFV核蛋白的完整开放阅读框，并作为一种可能的候选疫苗进行了研究。在转染的幼仓鼠肾细胞中对该复制子的CCHFV RNA转录和重组蛋白产生进行了表征。插入质粒DNA（pSinCCHF-52S）中的编码CCHFV核蛋白的复制子在转染细胞中指导CCHFV RNA的转录。用pSinCCHF-52S免疫的NIH-III杂合小鼠产生了CCHFV IgG特异性抗体，与IgG1相比，IgG2a水平显著更高。用pSinCCHF-52S免疫的小鼠的脾细胞分泌IFN-γ和IL-2，IL-6或IL-10水平较低，且不分泌IL-4。在 mock免疫小鼠的脾细胞中未检测到特异性细胞因子产生（<0.05）。因此，我们的研究证明了辛德毕斯病毒载体表达CCHFV核蛋白及其在小鼠中的免疫原性。细胞因子产生谱和抗体谱表明主要是抗CCHFV免疫反应的Th1型。有必要在对CCHFV易感的动物中进行进一步研究，以确定诱导的免疫反应是否具有保护性。
