Wichgers Schreur Paul J, van Keulen Lucien, Kant Jet, Kortekaas Jeroen
Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands.
Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands.
Vaccine. 2017 May 25;35(23):3123-3128. doi: 10.1016/j.vaccine.2017.04.024. Epub 2017 Apr 27.
Rift Valley fever virus (RVFV) causes severe and recurrent outbreaks on the African continent and the Arabian Peninsula and continues to expand its habitat. This mosquito-borne virus, belonging to the genus Phlebovirus of the family Bunyaviridae contains a tri-segmented negative-strand RNA genome. Previously, we developed four-segmented RVFV (RVFV-4s) variants by splitting the M-genome segment into two M-type segments each encoding one of the structural glycoproteins; Gn or Gc. Vaccination/challenge experiments with mice and lambs subsequently showed that RVFV-4s induces protective immunity against wild-type virus infection after a single administration. To demonstrate the unprecedented safety of RVFV-4s, we here report that the virus does not cause encephalitis after intranasal inoculation of mice. A study with pregnant ewes subsequently revealed that RVFV-4s does not cause viremia and does not cross the ovine placental barrier, as evidenced by the absence of teratogenic effects and virus in the blood and organs of the fetuses. Altogether, these results show that the RVFV-4s vaccine virus can be applied safely in pregnant ewes.
裂谷热病毒（RVFV）在非洲大陆和阿拉伯半岛引发严重且反复的疫情，并且其栖息地还在不断扩大。这种通过蚊子传播的病毒属于布尼亚病毒科白蛉病毒属，含有一个三段式负链RNA基因组。此前，我们通过将M基因组片段拆分为两个M型片段，每个片段编码一种结构糖蛋白（Gn或Gc），开发出了四段式RVFV（RVFV-4s）变体。随后对小鼠和羔羊进行的疫苗接种/攻毒实验表明，RVFV-4s单次给药后就能诱导产生针对野生型病毒感染的保护性免疫。为证明RVFV-4s前所未有的安全性，我们在此报告，该病毒经鼻内接种小鼠后不会引发脑炎。随后一项针对怀孕母羊的研究表明，RVFV-4s不会导致病毒血症，也不会穿过绵羊胎盘屏障，这一点在胎儿的血液和器官中未出现致畸效应和病毒得到了证明。总之，这些结果表明，RVFV-4s疫苗病毒可安全应用于怀孕母羊。
