Abstract：
Rift Valley fever (RVF) is a mosquito-borne zoonotic disease caused by RVF virus (RVFV). RVFV infections in humans are usually asymptomatic or associated with mild febrile illness, although more severe cases of haemorrhagic disease and encephalitis with high mortality also occur. Currently, there are no licensed human vaccines available. The safety and efficacy of a genetically engineered four-segmented RVFV variant (hRVFV-4s) as a potential live-attenuated human vaccine has been tested successfully in mice, ruminants, and marmosets though the correlates of protection of this vaccine are still largely unknown. In the present study, we have assessed hRVFV-4s-induced humoral and cellular immunity in a mouse model of RVFV infection. Our results confirm that a single dose of hRVFV-4s is highly efficient in protecting naïve mice from developing severe disease following intraperitoneal challenge with a highly virulent RVFV strain and data show that virus neutralizing (VN) serum antibody titres in a prime-boost regimen are significantly higher compared to the single dose. Subsequently, VN antibodies from prime-boost-vaccinated recipients were shown to be protective when transferred to naïve mice. In addition, hRVFV-4s vaccination induced a significant virus-specific T cell response as shown by IFN-γ ELISpot assay, though these T cells did not provide significant protection upon passive transfer to naïve recipient mice. Collectively, this study highlights hRVFV-4s-induced VN antibodies as a major correlate of protection against lethal RVFV infection.
摘要：
摘要裂谷热（RVF）是由RVF病毒（RVFV）引起的蚊子传播的人畜共患疾病。人类的RVFV感染通常无症状或与轻度发热疾病有关，尽管也会发生更严重的出血性疾病和脑炎，死亡率很高。目前,没有获得许可的人类疫苗。已在小鼠中成功测试了基因工程四段RVFV变体（hRVFV-4s）作为潜在的减毒活人疫苗的安全性和有效性。反刍动物,尽管这种疫苗的保护作用的相关性在很大程度上仍然未知。在本研究中，我们评估了hRVFV-4s在RVFV感染小鼠模型中诱导的体液和细胞免疫。我们的结果证实，单剂量的hRVFV-4s在用高毒力的RVFV毒株腹膜内攻击后保护幼稚小鼠免于发展严重疾病方面非常有效，并且数据显示，初免-加强方案中的病毒中和（VN）血清抗体滴度明显高于单剂量。随后，来自初免-加强免疫接种的受体的VN抗体在转移到未处理的小鼠时显示出保护性。此外,hRVFV-4s疫苗接种诱导了显着的病毒特异性T细胞应答，如IFN-γELISpot测定所示，尽管这些T细胞在被动转移到原始受体小鼠后没有提供显著的保护。总的来说，这项研究强调了hRVFV-4s诱导的VN抗体是针对致死性RVFV感染的保护作用的主要相关因素。
