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基因改造狂犬病病毒载体基里夫谷热病毒疫苗对小鼠安全有效。

Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice.

机构信息

College of Wildlife and Protected Areas, Northeast Forestry University, Harbin 150040, China.

Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China.

出版信息

Viruses. 2019 Oct 8;11(10):919. doi: 10.3390/v11100919.

Abstract

Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a > 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (T) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections.

摘要

裂谷热病毒(RVFV)引起裂谷热(RVF),是一种蚊媒传播的人畜共患病病原体,可导致牲畜和人类严重的发病率和死亡率。RVF 是世界卫生组织(WHO)的优先疾病,与狂犬病一起,是非洲的主要卫生负担。在这里,我们介绍了一种灭活重组 RVFV 和狂犬病病毒(RABV)疫苗候选物(rSRV9-eGn)的开发和特性。rSRV9-eGn 免疫可刺激 RVFV 特异性 IgG 抗体的产生,并在小鼠中诱导体液和细胞免疫,但不诱导中和抗体的产生。IgG1 和 IgG2a 是通过 IgG 亚型检测观察到的主要同种型,未检测到 IgG3 抗体。IgG1/IgG2a>1 的比值表明存在 2 型体液免疫反应。有效的疫苗旨在建立记忆 T 细胞的长期群体,rSRV9-eGn 免疫后,小鼠在增殖 T 细胞群体中产生记忆细胞,效应记忆 T 细胞(T)为主要群体。由于缺乏预防性治疗实验,无法预测这种疫苗是否可以在仅诱导高滴度抗 RVFV IgG 抗体而不诱导中和抗体的情况下保护动物免受 RVFV 感染,因此需要进一步验证保护确认。然而,这种以 RABV 为载体设计的 RVFV 疫苗为预防 RVFV 和 RABV 感染的疫苗的开发提供了思路。

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