Warimwe George M, Gesharisha Joseph, Carr B Veronica, Otieno Simeon, Otingah Kennedy, Wright Danny, Charleston Bryan, Okoth Edward, Elena Lopez-Gil, Lorenzo Gema, Ayman El-Behiry, Alharbi Naif K, Al-dubaib Musaad A, Brun Alejandro, Gilbert Sarah C, Nene Vishvanath, Hill Adrian V S
The Jenner Institute, University of Oxford, Oxford, UK.
Centre for Research in Therapeutic Sciences and, Institute for Healthcare Management, Strathmore University, Nairobi, Kenya.
Sci Rep. 2016 Feb 5;6:20617. doi: 10.1038/srep20617.
Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.
裂谷热病毒(RVFV)在非洲和阿拉伯半岛引发急性危及生命的人畜疾病的反复爆发。目前尚无获批用于人类的疫苗,而广泛用于牲畜的疫苗存在重大安全隐患。一种“同一健康”疫苗研发方法,即针对多种易感物种共同研发同一种疫苗,是针对RVFV的一种有吸引力的策略。在此,我们利用具有既定人畜安全概况的复制缺陷型黑猩猩腺病毒疫苗平台ChAdOx1,来研发一种可同时用于牲畜和人类以对抗RVFV的疫苗。我们表明,用编码RVFV包膜糖蛋白的ChAdOx1-GnGc疫苗进行单剂量免疫可诱导产生高滴度的RVFV中和抗体,并在该病毒最易感的天然靶标物种——绵羊、山羊和牛中提供针对RVFV攻击的坚实保护。此外,我们证明ChAdOx1-GnGc疫苗接种可在单峰骆驼中诱导产生RVFV中和抗体,进一步说明了复制缺陷型黑猩猩腺病毒疫苗平台的效力。因此,ChAdOx1-GnGc值得在人类临床试验中进行评估,并有可能满足尚未满足的人畜疫苗需求。