MHCI trafficking signal‐based mRNA vaccines strengthening immune protection against RNA viruses

Yupei Zhang; Songhui Zhai; Shugang Qin; Yuting Chen; Kepan Chen; Zhiying Huang; Xing Lan; Yaoyao Luo; Guohong Li; Hao Li; Xi He; Meiwan Chen; Zhongwei Zhang; Xingchen Peng; Xin Jiang; Hai Huang; Xiangrong Song

doi:10.1002/btm2.10709

Bioengineering & Translational Medicine (Jan 2025)

MHCI trafficking signal‐based mRNA vaccines strengthening immune protection against RNA viruses

Yupei Zhang,
Songhui Zhai,
Shugang Qin,
Yuting Chen,
Kepan Chen,
Zhiying Huang,
Xing Lan,
Yaoyao Luo,
Guohong Li,
Hao Li,
Xi He,
Meiwan Chen,
Zhongwei Zhang,
Xingchen Peng,
Xin Jiang,
Hai Huang,
Xiangrong Song

Affiliations

Yupei Zhang: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Songhui Zhai: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Shugang Qin: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Yuting Chen: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Kepan Chen: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Zhiying Huang: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Xing Lan: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Yaoyao Luo: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Guohong Li: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Hao Li: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Xi He: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Meiwan Chen: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau Macau China
Zhongwei Zhang: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Xingchen Peng: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Xin Jiang: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Hai Huang: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China
Xiangrong Song: Department of Critical Care Medicine Frontiers Science Center for Disease‐related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu Sichuan China

DOI: https://doi.org/10.1002/btm2.10709
Journal volume & issue: Vol. 10, no. 1
pp. n/a – n/a

Abstract

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Abstract The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD‐based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD‐based mRNA vaccines encoding binding receptor‐binding domain (RBD) of SARS‐CoV‐2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.

Published in Bioengineering & Translational Medicine

ISSN: 2380-6761 (Online)
Publisher: Wiley
Country of publisher: United States
LCC subjects: Technology: Chemical technology: Chemical engineering; Technology: Chemical technology: Biotechnology; Medicine: Therapeutics. Pharmacology
Website: https://aiche.onlinelibrary.wiley.com/journal/23806761

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