Attenuated Getah virus confers protection against multiple arthritogenic alphaviruses.

IF 5.5 1区 医学 Q1 MICROBIOLOGY PLoS Pathogens Pub Date : 2024-11-18 DOI:10.1371/journal.ppat.1012700
Zhiwen Jiang, Andres Merits, Ying Qin, Gang Xing, Letian Zhang, Jie Chen, Ningning Wang, Margus Varjak, Xiaofeng Zhai, Dongyan Li, Wanjie Song, Shuo Su
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Abstract

Alphaviruses are important arthropod-transmitted pathogens of humans and livestock. Getah virus (GETV) is an arthritogenic alphavirus that causes disease in horses and piglets; it also poses a potential threat to humans. A live attenuated vaccine candidate named GETV-3ΔS2-CM1, harbouring a deletion in nonstructural protein 3 and substitutions in the capsid protein, is genetically stable and exhibits robust immunogenicity. It was shown to confer passive protection to piglets born to immunized sows. In mice, a single dose of GETV-3ΔS2-CM1 protected against infection with different strains of GETV, Semliki Forest virus, Ross River virus, o'nyong'nyong virus, chikungunya virus, and Barmah Forest virus. Chimaeras based on the GETV-3ΔS2-CM1 backbone maintained both the attenuated phenotype and high immunogenicity. The safety, efficacy, and ability to induce protection against multiple alphaviruses highlights the potential of GETV-3ΔS2-CM1 and chimaeras using this backbone as promising vaccine candidates. By contributing simultaneously to the wellbeing of animals and humans, our universal next generation vaccine strategy helps to achieve "One Health" goals.

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减毒的 Getah 病毒能抵御多种致关节炎的阿尔巴病毒。
阿尔法病毒是人类和牲畜的重要节肢动物传播病原体。Getah病毒(GETV)是一种关节炎型α-病毒,可导致马和仔猪发病,对人类也构成潜在威胁。一种名为 GETV-3ΔS2-CM1 的减毒活疫苗候选株含有非结构蛋白 3 的缺失和荚膜蛋白的替代物,具有遗传稳定性和强大的免疫原性。实验证明,它能为免疫母猪所产的仔猪提供被动保护。在小鼠体内,单剂量的 GETV-3ΔS2-CM1 对不同毒株的 GETV、Semliki Forest 病毒、Ross River 病毒、o'nyong'nyong 病毒、基孔肯雅病毒和 Barmah Forest 病毒感染均有保护作用。基于 GETV-3ΔS2-CM1 骨架的嵌合体既保持了减毒表型,又具有高免疫原性。GETV-3ΔS2-CM1的安全性、有效性和诱导对多种α-病毒的保护能力,凸显了GETV-3ΔS2-CM1和使用这种骨架的嵌合体作为候选疫苗的潜力。通过同时为动物和人类的健康做出贡献,我们的通用下一代疫苗战略有助于实现 "同一健康 "目标。
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来源期刊
PLoS Pathogens
PLoS Pathogens MICROBIOLOGY-PARASITOLOGY
自引率
3.00%
发文量
598
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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