PDF(Pubmed)
Abstract：
Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots.
摘要：
裂谷热（RVF）是一种蚊子传播的人畜共患病毒性疾病，在非洲和中东流行。减毒活活RVF疫苗已被研究用于兽医和人类使用,因为它们具有强的免疫原性和成本效益的制造。减毒MP-12活疫苗已在美国有条件地批准用于兽医。和下一代减毒RVF活疫苗候选物正在积极研究中。评估疫苗种子或批次的毒力表型对于管理疫苗安全性至关重要。以前,断奶前19天大的近交CD1小鼠已用于评估MP-12菌株。本研究旨在表征19日龄近交C57BL/6小鼠中三种减毒活疫苗株的相对毒力：重组MP-12（rMP-12），RVax-1和ΔNS-ΔNSm-rZH501菌株。尽管这种小鼠模型没有显示出剂量依赖性的发病机制，死于感染的小鼠表现出明显的脑病理学。感染ΔNS-ΔNSm-rZH501的小鼠显示与感染的神经元相关的炎症细胞浸润，和在病毒感染细胞周围形成的局灶性病变。相比之下,感染rMP-12或RVax-1的小鼠在大脑中显示出炎性细胞的最小关联，然而，病毒扩散。断奶前模型可能可用于评估宿主对减毒RVFV菌株的反应，尽管可能需要进一步细化以定量不同RVFV毒株或疫苗批次之间的毒力。
