Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats
Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats
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DOI：
10.1038/s41541-019-0138-0
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发表时间：
2019-10-18
期刊：
影响因子：
9.2
通讯作者：
Warimwe, George M.
中科院分区：
文献类型：
--
作者：
Stedman, Anna;Wright, Daniel;Warimwe, George M.
裂谷热病毒（RVFV）是一种人畜共患蚊媒病毒，1930年首次在肯尼亚发现，此后在非洲大部分地区和阿拉伯半岛蔓延成为地方病。裂谷热（裂谷热）引起反复爆发的发热性疾病，与高死亡率和妊娠期不良结局有关，包括牲畜的胎儿畸形、自然流产和死胎，并与人类的流产有关。没有疫苗可供人类使用，那些被许可用于兽医的疫苗有潜在的缺点，包括可能禁忌在怀孕期间使用的残留毒力。为了解决这一差距，我们以前开发了一种猿腺病毒载体疫苗，ChAdOx1 RVF，编码RVFV包膜糖蛋白。ChAdOx1裂谷热疫苗对未怀孕牲畜具有完全的裂谷热保护作用，目前正在开发供人类使用。在这里，我们现在证明，当给予怀孕的绵羊和山羊时，ChAdOx1 RVF是安全的，可产生高滴度的RVFV中和抗体，并提供针对病毒血症和胎儿丢失的保护，尽管这种保护对山羊来说并不那么强大。此外，我们提供了一个描述RVFV的挑战，在怀孕的山羊和对比，在怀孕的绵羊观察到的病理。总之，我们的数据进一步支持正在进行的用于牲畜和人类的ChAdOx1裂谷热疫苗的开发。
Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy-including foetal malformations, spontaneous abortion and stillbirths-in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.