Sterilized protective immunity induced by DAM and DAM⁺ in mouse models for both VACV and MPXV.

IF 18.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Bulletin Pub Date : 2025-05-14 DOI:10.1016/j.scib.2025.05.013

Zhengrong Gao, Tingting Zheng, Jiahao Wu, Haoyi Ding, Jia Lu, Jiahui Si, Yuze Xu, Hao Liu, Guocan Yu, Renyi Ma, Jianxun Qi, Yunfei Zhao, Jiaqi Ran, Qihui Wang, Xiaopeng Ma, Zhida Liu, Han Wang, George Fu Gao

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引用次数: 0

Abstract

The increasing prevalence of mpox calls for the development of safer and more accessible next-generation vaccines. Based on a structure-guided "two-in-one" immunogen design strategy, we have previously developed an innovative protein-based monkeypox virus (MPXV) vaccine, DAM, which addresses the issues of imbalanced bioavailability associated with cocktail vaccines and elicits superior antiviral immunity with a safety profile. In this study, we iteratively designed two "four-in-one" chimeric immunogens, DAM⁺s, using four MPXV antigens, M1, A29, A35, and B6. Although DAM⁺s elicited broader immune responses against four antigens, no additional benefit in either in vitro neutralization or in vivo protection against poxviruses was detected compared to DAM. Notably, vaccination-related tissue damage was observed in the live virus vaccine group, whereas all protein-based vaccines showed better safety and protection against lethal vaccinia virus (VACV) challenge. Together, these further demonstrate that DAM, with a minimal protein subunit of two components, is a promising immunogen to be further clinically developed.

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DAM和DAM+在小鼠模型中对VACV和MPXV诱导的无菌保护性免疫。

mpox的日益流行要求开发更安全、更容易获得的下一代疫苗。基于结构导向的“二合一”免疫原设计策略，我们先前开发了一种创新的基于蛋白质的猴痘病毒（MPXV）疫苗DAM，该疫苗解决了与鸡尾酒疫苗相关的生物利用度不平衡问题，并引发了具有安全性的卓越抗病毒免疫。在这项研究中，我们迭代设计了两个“四合一”嵌合免疫原DAM+s，使用四种MPXV抗原M1、A29、A35和B6。虽然DAM+s对四种抗原引起了更广泛的免疫应答，但与DAM相比，在体外中和或体内保护痘病毒方面没有发现额外的益处。值得注意的是，在活病毒疫苗组中观察到疫苗相关的组织损伤，而所有基于蛋白质的疫苗都显示出更好的安全性和对致命痘苗病毒（VACV）攻击的保护。总之，这些进一步证明了DAM是一种有前途的免疫原，具有两种成分的最小蛋白质亚基，值得进一步临床开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Bulletin MULTIDISCIPLINARY SCIENCES-

CiteScore

24.60

自引率

2.10%

发文量

8092

期刊介绍： Science Bulletin (Sci. Bull., formerly known as Chinese Science Bulletin) is a multidisciplinary academic journal supervised by the Chinese Academy of Sciences (CAS) and co-sponsored by the CAS and the National Natural Science Foundation of China (NSFC). Sci. Bull. is a semi-monthly international journal publishing high-caliber peer-reviewed research on a broad range of natural sciences and high-tech fields on the basis of its originality, scientific significance and whether it is of general interest. In addition, we are committed to serving the scientific community with immediate, authoritative news and valuable insights into upcoming trends around the globe.