RVFV detection in organs.

Rift Valley fever (RVF) is an important zoonotic viral disease affecting several species of domestic and wild ruminants, causing major economic losses and dozens of human deaths in various geographical areas of Africa, where it is endemic. Although it is not present in Europe, there is a risk of its introduction and spread linked to globalisation and climate change. At present, the only measure that could help to prevent the disease is vaccination of flocks in areas at risk of RVF. Available live attenuated vaccines are an effective means of controlling the disease, but their use is often questioned due to residual virulence, particularly in susceptible hosts such as pregnant sheep. On the other hand, no vaccine is currently licensed for use in humans. The development of safe and effective vaccines is therefore a major area of research. In previous studies, we selected under selective mutagenic pressure a highly attenuated RVFV 56/74 virus variant called 40Fp8. This virus showed an extremely attenuated phenotype in both wild-type and immunodeficient A129 (IFNARKO) mice, yet was still able to induce protective immunity after a single inoculation, thus supporting its use as a safe, live attenuated vaccine. To further investigate its safety, in this work we have analysed the attenuation level of 40Fp8 in immunosuppressed mice (A129) when administered by the intranasal route, and compared it with other attenuated RVF viruses that are the basis of vaccines in use or in development. Our results show that 40Fp8 has a much higher attenuated level than these other viruses and confirm its potential as a candidate for safe RVF vaccine development.

裂谷热（Rift Valley fever, RVF）是一种重要的人畜共患病毒性疾病，可侵染多种家养与野生反刍动物，在非洲的地方性流行区域内可引发严重经济损失并造成数十人死亡。尽管欧洲目前暂无该病的流行记录，但全球化与气候变化带来的关联风险可能导致该病传入并扩散。当前，预防该病的唯一可行措施是在RVF风险区域对畜群实施疫苗接种。现有减毒活疫苗（live attenuated vaccines）是控制该病的有效手段，但由于其存在残余毒力，这类疫苗的应用常受到质疑，尤其是在妊娠绵羊等易感宿主中。另一方面，目前尚无获批用于人类的RVF疫苗。因此，研发安全有效的疫苗是当前的核心研究方向。在既往研究中，我们团队通过选择性诱变压力（selective mutagenic pressure）筛选出一株命名为40Fp8的高减毒RVFV 56/74病毒变异株。该病毒在野生型及免疫缺陷A129（IFNAR敲除，IFNARKO）小鼠中均展现出极强的减毒表型，但单次接种后仍可诱导机体产生保护性免疫，证实其可作为安全的减毒活疫苗候选株。为进一步探究其安全性，本研究通过经鼻（intranasal）途径接种免疫抑制A129小鼠，分析了40Fp8的减毒水平，并将其与其他作为现有或在研疫苗基础的减毒RVF病毒进行了对比。结果显示，40Fp8的减毒水平远高于上述其他病毒，进一步证实了其作为安全RVF疫苗研发候选株的潜力。