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开发针对 Mayaro 病毒的病毒载体疫苗和基于病毒复制子颗粒的中和测定法。

Development of Viral-Vectored Vaccines and Virus Replicon Particle-Based Neutralisation Assay against Mayaro Virus.

机构信息

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7BN, UK.

Institute of Virology, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

出版信息

Int J Mol Sci. 2022 Apr 7;23(8):4105. doi: 10.3390/ijms23084105.

Abstract

Mayaro virus (MAYV) is an emerging alphavirus causing acute febrile illness associated with chronic polyarthralgia. Although MAYV is currently restricted to tropical regions in South America around the Amazon basin, it has the potential to spread globally by species mosquitoes. In addition, there are currently no specific therapeutics or licenced vaccines against MAYV infection. We have previously shown that an adenovirus based Mayaro vaccine (ChAdOx1 May) was able to provide full protection against MAYV challenge in vaccinated A129 mice and induced high neutralising antibody titres. In this study, we have constructed a replication deficient simian adenovirus (ChAdOx2) and a Modified Ankara Virus (MVA) based vaccine expressing the MAYV structural cassette (sMAYV) similar to ChAdOx1 May, and characterised recombinant MAYV E2 glycoprotein expressed in a mammalian system for immune monitoring. We demonstrate that ChAdOx2 May was able to induce high antibody titres similar to ChAdOx1 May, and MVA May was shown to be an effective boosting strategy following prime vaccination with ChAdOx1 or ChAdOx2 May. In order to measure MAYV neutralising ability, we have developed a virus replicon particle-based neutralisation assay which effectively detected neutralising antibodies against MAYV. In summary, our study indicates the potential for further clinical development of the viral vectored MAYV vaccines against MAYV infections.

摘要

马亚罗病毒(MAYV)是一种新兴的甲病毒,可引起与慢性多关节痛相关的急性发热性疾病。尽管 MAYV 目前仅限于南美洲亚马逊流域周围的热带地区,但它有可能通过 种蚊子在全球范围内传播。此外,目前尚无针对 MAYV 感染的特定治疗方法或许可疫苗。我们之前曾表明,一种基于腺病毒的马亚罗疫苗(ChAdOx1 May)能够在接种 A129 小鼠中提供针对 MAYV 挑战的完全保护,并诱导高中和抗体滴度。在这项研究中,我们构建了一种复制缺陷的猴腺病毒(ChAdOx2)和一种基于 Modified Ankara Virus(MVA)的疫苗,该疫苗表达与 ChAdOx1 May 相似的 MAYV 结构盒(sMAYV),并在哺乳动物系统中对 MAYV E2 糖蛋白进行了免疫监测。我们证明 ChAdOx2 May 能够诱导与 ChAdOx1 May 相似的高抗体滴度,并且 MVA May 被证明是在用 ChAdOx1 或 ChAdOx2 May 进行初次接种后的有效增强策略。为了测量 MAYV 的中和能力,我们开发了一种基于病毒复制子颗粒的中和测定法,该测定法有效地检测了针对 MAYV 的中和抗体。总之,我们的研究表明,针对 MAYV 感染的病毒载体 MAYV 疫苗具有进一步临床开发的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/9026931/7ccb6ede768f/ijms-23-04105-g001.jpg

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