Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA.
Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
Vaccine. 2020 Apr 9;38(17):3378-3386. doi: 10.1016/j.vaccine.2020.02.007. Epub 2020 Feb 19.
Live-attenuated V4020 vaccine for Venezuelan equine encephalitis virus (VEEV) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol challenge with wild-type VEEV. The genomic RNA of V4020 vaccine virus was encoded in the pMG4020 plasmid under control of the CMV promoter and contained the capsid gene downstream from the glycoprotein genes. It also included attenuating mutations from the VEE TC83 vaccine, with E2-120Arg substitution genetically engineered to prevent reversion mutations. The population of V4020 vaccine virus derived from pMG4020-transfected Vero cells was characterized by next generation sequencing (NGS) and indicated no detectable genetic reversions. Cynomolgus macaques were vaccinated with V4020 vaccine virus. After one or two vaccinations including by intramuscular route, high levels of virus-neutralizing antibodies were confirmed with no viremia or apparent adverse reactions to vaccinations. The protective effect of vaccination was evaluated using an aerosol challenge with VEEV. After challenge, macaques had no detectable viremia, demonstrating a protective effect of vaccination with live V4020 VEEV vaccine.
一种含有病毒结构基因减弱重排的活病毒委内瑞拉马脑炎病毒（VEEV）V4020 疫苗在非人灵长类动物模型中进行了免疫原性和针对野生型 VEEV 气溶胶挑战的保护效力评估。V4020 疫苗病毒的基因组 RNA 由 CMV 启动子控制下的 pMG4020 质粒编码，并包含在糖蛋白基因下游的衣壳基因。它还包含来自 VEE TC83 疫苗的减弱突变，E2-120Arg 取代基因工程以防止回复突变。源自 pMG4020 转染的 Vero 细胞的 V4020 疫苗病毒群体通过下一代测序（NGS）进行了表征，表明没有检测到可遗传的回复突变。食蟹猴用 V4020 疫苗病毒接种。接种一次或两次，包括肌肉内途径接种后，用病毒中和抗体检测证实了高水平的抗体，没有病毒血症或明显的疫苗接种不良反应。通过 VEEV 气溶胶挑战评估了疫苗接种的保护效果。在挑战后，猴子没有检测到可检测的病毒血症，表明活 V4020 VEEV 疫苗接种具有保护作用。
