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A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-Cell immunogen shows enhanced immunogenicity in mice

机译:表达口蹄疫病毒衣壳蛋白和T细胞免疫原的假杆状病毒显示出增强的小鼠免疫原性

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Background Foot-and-mouth disease (FMD) is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must. Methods In the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV) under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE), and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine. Results Indirect immunofluorescence assay (IFA) and indirect sandwich-ELISA (IS-ELISA) showed both recombinant baculoviruses (with or without T-cell epitopes) were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ). Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P P Conclusions These results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.
机译:背景技术口蹄疫(FMD)是一种高度传染性的牲畜疾病,在偶蹄类动物中造成严重的经济损失。疫苗接种仍然是发展中国家控制口蹄疫的一项主要战略。目前,FMDV灭活疫苗已在许多国家使用,但成功和安全性有限。必须开发一种新型有效疫苗。方法在本研究中,两种重组假型杆状病毒,一种在巨细胞病毒立即早期增强子/启动子(CMV-IE)的控制下表达口蹄疫病毒(FMDV)的衣壳,另一种在壳状病毒中表达。构建了CAG启动子下的T细胞免疫原编码区,并在哺乳动物细胞中表征了它们的表达。另外,研究了它们在小鼠模型中的免疫原性。将假型杆状病毒诱导的体液和细胞介导的免疫反应与灭活疫苗进行了比较。结果间接免疫荧光法(IFA)和间接三明治ELISA(IS-ELISA)显示重组杆状病毒(有或没有T细胞表位)均能有效转导并在BHK-21细胞中表达靶蛋白。在小鼠中,肌肉内接种1×10 9 或1×10 10 PFU /小鼠的重组体可诱导产生FMDV特异性中和抗体和γ-干扰素(IFN-γ)。 )。此外,重组杆状病毒具有T细胞表位的免疫原性比不含T细胞表位的重组体具有更好的免疫原性,这可以通过IFN-γ的产生显着增强来证明(PP结论)这些结果表明,假型杆状病毒介导的基因传递可能是开发A型抗原性杆状病毒的另一种策略。针对FMDV感染的新一代疫苗。

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