State Key Laboratory of Veterinary Etiological Biology and OIE/CHINA National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, PR China; College of Animal Science, Yangtze University, Jingzhou, Hubei Province, 434023, PR China.
State Key Laboratory of Veterinary Etiological Biology and OIE/CHINA National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, PR China.
Microb Pathog. 2020 Jun;143:104130. doi: 10.1016/j.micpath.2020.104130. Epub 2020 Mar 9.
Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects cloven-hoofed animals. Virus-like particles (VLPs) can induce a robust immune response and deliver DNA and small molecules. In this study, a VLP-harboring pcDNA3.1/P12A3C plasmid was generated, and the protective immune response was characterized. Guinea pigs were injected with VLPs, naked DNA vaccine, DNA-loaded VLPs, or phosphate-buffered saline twice subcutaneously at four-week intervals. Results demonstrated that the VLPs protected the naked DNA from DNase degeneration and delivered the DNA into the cells in vitro. The DNA-loaded VLPs and the VLPs alone induced a similar level of specific antibodies (P > 0.05) except at 49 dpv (P < 0.05). The difference in interferon-γ was consistent with that in specific antibodies. The levels of neutralizing antibodies induced by the DNA-loaded VLPs were significantly higher than those of other samples (P < 0.01). Similarly, the lymphocyte proliferation by using DNA-loaded VLPs was significantly higher than those using other formulas after booster immunization. Vaccination with DNA-loaded VLPs provided higher protection (100%) against viral challenge compared with vaccination with VLPs (75%) and DNA vaccine (25%). This study suggested that VLPs can be used as a delivery carrier for DNA vaccine. In turn, the DNA vaccine can enhance the immune response and prolong the serological duration of the VLP vaccine. This phenomenon contributes in providing complete protection against the FMDV challenge in guinea pigs and can be valuable in exploring novel nonreplicating vaccines and controlling FMD in endemic countries worldwide.
口蹄疫病毒(FMDV)是一种高度传染性疾病的病原体,会影响偶蹄类动物。病毒样颗粒(VLPs)可以诱导强烈的免疫反应,并能递送 DNA 和小分子。在这项研究中,生成了一种携带 pcDNA3.1/P12A3C 质粒的 VLP,并对其保护性免疫反应进行了表征。豚鼠通过皮下注射 VLP、裸 DNA 疫苗、负载 DNA 的 VLP 或磷酸盐缓冲盐水,每隔四周注射两次。结果表明,VLP 可以保护裸 DNA 免受 DNA 酶的降解,并将 DNA 递送到细胞中。负载 DNA 的 VLP 和单独的 VLP 诱导了相似水平的特异性抗体(P>0.05),但在 49 天(P<0.05)时除外。干扰素-γ的差异与特异性抗体的差异一致。负载 DNA 的 VLP 诱导的中和抗体水平明显高于其他样本(P<0.01)。同样,在加强免疫后,使用负载 DNA 的 VLP 进行淋巴细胞增殖的水平明显高于其他配方。与 VLP 疫苗(75%)和 DNA 疫苗(25%)相比,负载 DNA 的 VLP 疫苗接种提供了更高的保护(100%),可以抵抗病毒的攻击。本研究表明,VLP 可以作为 DNA 疫苗的递送载体。反过来,DNA 疫苗可以增强免疫反应并延长 VLP 疫苗的血清学持续时间。这种现象有助于在豚鼠中提供针对 FMDV 攻击的完全保护,并可以为探索新型非复制疫苗和控制全球流行国家的 FMD 提供有价值的参考。