裂谷热病毒(RVFV)在人类和有蹄类动物中引起严重疾病。这种病毒可以通过蚊子传播,直接接触受感染的组织或液体,或者气溶胶,使其成为没有批准的疫苗或治疗方法的重大生物威胁。在本文中,我们描述了DEF201的评估,DEF201是一种腺病毒载体干扰素α,它解决了重组干扰素α蛋白的局限性(成本,半衰期短),作为致命仓鼠RVFV挑战模型中的暴露前和暴露后治疗。鼻内递送DEF201以刺激粘膜免疫并有效地绕过对载体的任何预先存在的免疫。从攻击前1或7天施用的单剂量DEF201观察到针对RVFV感染的完全保护,而所有对照动物在感染后3天内死亡。在攻击前两周施用的治疗的功效是有限的。曝光后,当在30分钟或6小时给药时,DEF201能够赋予显著的保护作用,但不是在RVFV挑战后24小时。保护与血清和组织病毒载量的降低有关。我们的发现表明,DEF201可能是对抗RVFV感染的有用对策,并进一步证明了其刺激单剂量保护性免疫的广谱能力。
Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201, an adenovirus-vectored interferon alpha which addresses the limitations of recombinant interferon alpha protein (cost, short half-life), as a pre- and post-exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered intranasally to stimulate mucosal immunity and effectively bypass any pre-existing immunity to the vector. Complete protection against RVFV infection was observed from a single dose of DEF201 administered one or seven days prior to challenge while all control animals succumbed within three days of infection. Efficacy of treatment administered two weeks prior to challenge was limited. Post‑exposure, DEF201 was able to confer significant protection when dosed at 30 min or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with reductions in serum and tissue viral loads. Our findings suggest that DEF201 may be a useful countermeasure against RVFV infection and further demonstrates its broad-spectrum capacity to stimulate single dose protective immunity.