首页> 美国卫生研究院文献>Viruses >Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV
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Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV

机译:重组嵌合传播性胃肠炎病毒(TGEV)-猪流行性腹泻病毒(PEDV)病毒可抵抗强毒PEDV

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摘要

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide. Although both inactivated and live attenuated vaccines have been extensively used, the emergence of highly virulent strains and the recurrent outbreaks even in vaccinated farms highlight the need of effective vaccines. Engineering of genetically defined live attenuated vaccines is a rational approach for novel vaccine development. In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. This virus (rTGEV-RS-SPEDV) was attenuated in highly-sensitive five-day-old piglets, as infected animals did not lose weight and none of them died. In addition, the virus caused very minor tissue damage compared with a virulent virus. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). The rTGEV-RS-SPEDV virus protected against challenge with a virulent PEDV strain, reducing challenge virus titers in jejunum and leading to undetectable challenge virus RNA levels in feces. The rTGEV-RS-SPEDV virus induced a humoral immune response specific for PEDV, including neutralizing antibodies. Altogether, the data indicated that rTGEV-RS-SPEDV is a promising vaccine candidate against virulent PEDV infection.
机译:猪流行性腹泻病毒(PEDV)是一种肠道冠状病毒,在全球范围内导致猪群的高发病率和高死亡率。尽管灭活和减毒活疫苗均已广泛使用,但高毒力菌株的出现以及即使在接种疫苗的农场中也再次爆发,凸显了对有效疫苗的需求。基因定义的减毒活疫苗的工程设计是新型疫苗开发的合理方法。在这一方面,我们设计了基于传播性胃肠炎病毒(TGEV)基因组的减毒病毒,可表达来自强毒的美国(US)PEDV株的嵌合突突蛋白。该病毒(rTGEV-RS-SPEDV)在高度敏感的5日龄仔猪中减毒,因为被感染的动物没有体重减轻,也没有死亡。此外,与强毒病毒相比,该病毒对组织的损害很小。与用强力PEDV US株(PEDV-NVSL)感染诱导的保护作用相比,用于评估该病毒的保护作用的三周龄动物中的rTGEV-RS-SPEDV候选疫苗也有所减弱。 rTGEV-RS-SPEDV病毒可保护免受强毒PEDV株的攻击,降低空肠中的挑战病毒滴度,并导致粪便中无法检测到挑战病毒RNA水平。 rTGEV-RS-SPEDV病毒诱导了针对PEDV的体液免疫反应,包括中和抗体。总体而言,数据表明rTGEV-RS-SPEDV是针对有毒PEDV感染的有前途的候选疫苗。

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