Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
J Infect Dis. 2011 Nov;204 Suppl 3(Suppl 3):S1090-7. doi: 10.1093/infdis/jir379.
Outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central Africa and overlap with the occurrence of other infectious diseases of public health importance.
As a proof of concept we developed a bivalent recombinant vaccine based on vesicular stomatitis virus (VSV) expressing the Zaire ebolavirus (ZEBOV) and Andes virus (ANDV) glycoproteins (VSVΔG/Dual) and evaluated its protective efficacy in the common lethal Syrian hamster model. Hamsters were vaccinated with VSVΔG/Dual and were lethally challenged with ZEBOV or ANDV. Time to immunity and postexposure treatment were evaluated by immunizing hamsters at different times prior to and post ZEBOV challenge.
A single immunization with VSVΔG/Dual conferred complete and sterile protection against lethal ZEBOV and ANDV challenge. Complete protection was achieved with an immunization as close as 3 days prior to ZEBOV challenge, and 40% of the animals were even protected when treated with VSVΔG/Dual one day postchallenge. In comparison to the monovalent VSV vaccine, the bivalent vaccine has slightly reduced postexposure efficacy most likely due to its restricted lymphoid organ replication.
Bivalent VSV vectors are a feasible approach to vaccination against multiple pathogens.
丝状病毒出血热的爆发零星且不可预测地发生在中非的广大地区，与其他具有公共卫生重要性的传染病同时发生。
作为概念验证，我们开发了一种基于水疱性口炎病毒（VSV）的二价重组疫苗，该疫苗表达扎伊尔埃博拉病毒（ZEBOV）和安第斯病毒（ANDV）糖蛋白（VSVΔG/Dual），并在常见的致命叙利亚仓鼠模型中评估其保护效力。仓鼠用 VSVΔG/Dual 疫苗接种，并接受 ZEBOV 或 ANDV 的致死性攻击。通过在 ZEBOV 攻击之前和之后的不同时间点免疫仓鼠来评估免疫时间和暴露后治疗。
单次免疫 VSVΔG/Dual 可完全、无菌地预防致命的 ZEBOV 和 ANDV 攻击。在 ZEBOV 攻击前 3 天进行免疫即可实现完全保护，而在攻击后一天用 VSVΔG/Dual 治疗时，有 40%的动物甚至得到了保护。与单价 VSV 疫苗相比，二价疫苗的暴露后疗效略有降低，这可能是由于其限制了淋巴器官的复制。
双价 VSV 载体是针对多种病原体进行疫苗接种的可行方法。
