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为全球根除牛瘟量身定制的廉价疫苗和快速诊断试剂盒,以及向非洲和亚洲的技术转让。

Inexpensive vaccines and rapid diagnostic kits tailor-made for the global eradication of rinderpest, and technology transfer to Africa and Asia.

作者信息

Yilma T, Aziz F, Ahmad S, Jones L, Ngotho R, Wamwayi H, Beyene B, Yesus M, Egziabher B, Diop M, Sarr J, Verardi P

机构信息

International Laboratory of Molecular Biology for Tropical Disease Agents, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.

出版信息

Dev Biol (Basel). 2003;114:99-111.

Abstract

Rinderpest is an acute and highly contagious viral disease of ruminants, often resulting in greater than 90% mortality. We previously reported the development of first- and second-generation recombinant vaccinia virus vaccines which provide complete protection against rinderpest virus (RPV) and peste-des-petits ruminants virus (PPRV). These vaccines are safe even for immunodeficient mice and macaques with acquired immunodeficiency syndrome. We developed a third-generation recombinant vaccinia virus vaccine (v2RVFH) that expresses the fusion and haemagglutinin genes of RPV under strong synthetic vaccinia virus promoters. Cattle vaccinated intramuscularly with as little as 10(3) plaque-forming units (PFU) of v2RVFH were completely protected from rinderpest. Vaccinated animals did not develop pock lesions or transmit v2RVFH to contact animals. Cattle vaccinated with a standard dose of 10(8) PFU of v2RVFH developed long-term, sterilizing immunity against rinderpest. Thus, v2RVFH is safe, efficacious, heat stable, inexpensive, easily administered, and allows serological differentiation between vaccinated and infected animals. To aid in diagnosis and differentiation of vaccinated from infected animals, we developed indirect ELISAs (iELISAs) that use baculovirus-expressed RPV or PPRV nucleoprotein as coating antigens. A single larva contains enough viral antigen to test more than 10,000 serum samples, in duplicate. African scientists trained at the ILMB successfully transferred the iELISA kit technology to more than 30 countries in Africa, providing a model for technology transfer among developing countries. Vaccination with v2RVFH, in conjunction with the iELISA kits, greatly enhances the prospects for global eradication of rinderpest, as developing nations achieve independence in control efforts.

摘要

牛瘟是反刍动物的一种急性且高度传染性的病毒性疾病,通常导致超过90%的死亡率。我们之前报道了第一代和第二代重组痘苗病毒疫苗的研发,这些疫苗能提供针对牛瘟病毒(RPV)和小反刍兽疫病毒(PPRV)的完全保护。这些疫苗即使对免疫缺陷小鼠和患有获得性免疫缺陷综合征的猕猴也是安全的。我们研发了第三代重组痘苗病毒疫苗(v2RVFH),它在强合成痘苗病毒启动子的控制下表达RPV的融合基因和血凝素基因。用低至10³ 蚀斑形成单位(PFU)的v2RVFH进行肌肉注射免疫的牛完全受到了牛瘟的保护。接种疫苗的动物没有出现痘疱病变,也没有将v2RVFH传播给接触的动物。用标准剂量10⁸ PFU的v2RVFH接种的牛产生了针对牛瘟的长期、绝育免疫力。因此,v2RVFH安全、有效、热稳定、廉价、易于接种,并且能在接种和感染动物之间进行血清学区分。为了辅助诊断以及区分接种和感染动物,我们研发了间接酶联免疫吸附测定法(iELISA),该方法使用杆状病毒表达的RPV或PPRV核蛋白作为包被抗原。一条幼虫所含的病毒抗原足以对超过10000份血清样本进行一式两份的检测。在国际实验室医学研究所接受培训的非洲科学家成功地将iELISA试剂盒技术转让给了非洲的30多个国家,为发展中国家之间的技术转让提供了一个范例。随着发展中国家在防控工作中实现自主,使用v2RVFH进行疫苗接种并结合iELISA试剂盒,极大地增强了全球根除牛瘟的前景。

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