中国科学院微生物研究所高福课题组近日取得一项新成果。经过不懈努力，他们提出了DAM和DAM⁺在小鼠模型中对VACV和MPXV诱导的无菌保护性免疫。相关论文于2025年5月14日发表在《科学通报》杂志上。

基于结构导向的“二合一”免疫原设计策略，课题组先前开发了一种创新的基于蛋白质的MPXV疫苗DAM，它解决了与鸡尾酒疫苗相关的生物利用度不平衡的问题，并引发了具有安全性的卓越抗病毒免疫。在这项研究中，研究团队迭代设计了两种“合一”嵌合免疫原DAM⁺s，分别以它们的MPXV抗原M1、A29、A35和B6为主题。虽然DAM⁺s引发了针对其抗原的更广泛的免疫应答，但与DAM相比，在体外中和或体内对痘病毒主题的保护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。

据了解，mpox的日益流行要求开发更安全、更容易获得的下一代疫苗。

附：英文原文

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

Author: Zhida Liu e f, Han Wang h, George Fu Gao c

Issue&Volume: 2025/05/14

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 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 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.

DOI: 10.1016/j.scib.2025.05.013

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927325004979