裂谷热病毒(RVFV)是一种蚊子传播的病原体,具有重大的人类和兽医健康后果,在流行病中定期出现。RVFV在反刍动物中导致胎儿丢失和死亡,在人类中可导致肝脏和肾脏疾病,迟发性脑炎,视网膜炎,在某些情况下,严重的出血热。减毒活疫苗候选物(DDVax),是通过从临床分离株中删除毒力因子NSs和NSm而开发的,ZH501,并已被证明在啮齿动物中安全和免疫原性,怀孕的绵羊和非人灵长类动物。NSm的缺失也严重限制了蚊子的中肠感染并抑制了媒介传播。为了证明环境安全,这项研究调查了复制,与RVFVMP-12和ZH501株相比,口服暴露后DDVax在蚊子中的传播和传播效率。在用DDvax或MP-12接种的山羊喂食后7天,还在蚊子中测量感染和传播概况。我们假设DDVax会比其他RVFV菌株以显着更低的速率感染蚊子,由于缺乏NSm,传输不称职。Ae的曝光。埃及伊蚊和CX。与对照组相比,通过人工血粉对8log10斑块形成单位(PFU)/mlDDVax的tarsalis导致蚊子体内DDVax感染率显着降低。斑块测定表明感染性DDVax在Cx中的传播可忽略不计。tarsalis唾液(1/140采样),Ae中没有。埃及伊蚊唾液(0/120)。接种DDVax或MP-12的山羊的血清在接种后1、2或3天通过噬斑测定没有可检测到的感染性病毒。传染性病毒是,然而,从饲喂接种MP-12的山羊的伊蚊和库蚊体内回收(13.8%和4.6%,分别),但惊人的是,DDvax阳性蚊子的尸体大大减少(4%,0%,分别)。此外,DDVax在任何山羊喂养的蚊子中都没有传播到腿/翅膀上。总的来说,这些结果与有利的环境安全概况一致.
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen with significant human and veterinary health consequences that periodically emerges in epizootics. RVFV causes fetal loss and death in ruminants and in humans can lead to liver and renal disease, delayed-onset encephalitis, retinitis, and in some cases severe haemorrhagic fever. A live attenuated vaccine candidate (DDVax), was developed by the deletion of the virulence factors NSs and NSm from a clinical isolate, ZH501, and has proven safe and immunogenic in rodents, pregnant sheep and non-human primates. Deletion of NSm also severely restricted mosquito midgut infection and inhibited vector-borne transmission. To demonstrate environmental safety, this
study investigated the replication, dissemination and transmission efficiency of DDVax in mosquitoes following oral exposure compared to RVFV strains MP-12 and ZH501. Infection and dissemination profiles were also measured in mosquitoes 7 days after they fed on goats inoculated with DDvax or MP-12. We hypothesized that DDVax would infect mosquitoes at significantly lower rates than other RVFV strains and, due to lack of NSm, be transmission incompetent. Exposure of Ae. aegypti and Cx. tarsalis to 8 log10 plaque forming units (PFU)/ml DDVax by artificial bloodmeal resulted in significantly reduced DDVax infection rates in mosquito bodies compared to controls. Plaque assays indicated negligible transmission of infectious DDVax in Cx. tarsalis saliva (1/140 sampled) and none in Ae. aegypti saliva (0/120). Serum from goats inoculated with DDVax or MP-12 did not harbour detectable infectious virus by plaque assay at 1, 2 or 3 days post-inoculation. Infectious virus was, however, recovered from Aedes and Culex bodies that fed on goats vaccinated with MP-12 (13.8% and 4.6%, respectively), but strikingly, DDvax-positive mosquito bodies were greatly reduced (4%, and 0%, respectively). Furthermore, DDVax did not disseminate to legs/wings in any of the goat-fed mosquitoes. Collectively, these results are consistent with a beneficial environmental safety profile.