Improved mRNA-based RSV vaccine with PreF forming enveloped virus-like particles

Pengdi Chai; Yi Shi; Xiaoyan Li; Mengyao Yang; Xiafei Liu; Mei Liu; Junjie Yu; Xiaoxuan Yin; Dongwei Li; Ke Li; Xiangyu Kong; Qin Zhang; Hong Wang; Xiaoman Sun; Jinsong Li; Lili Li; Dandi Li; Lili Pang; Xuancheng Lu; Zhaojun Duan

doi:10.1038/s41541-025-01205-x

Improved mRNA-based RSV vaccine with PreF forming enveloped virus-like particles

NPJ Vaccines. 2025 Jul 12;10(1):152. doi: 10.1038/s41541-025-01205-x.

Authors

Pengdi Chai^#¹, Yi Shi^#¹, Xiaoyan Li^#², Mengyao Yang¹, Xiafei Liu³, Mei Liu², Junjie Yu¹, Xiaoxuan Yin¹, Dongwei Li¹, Ke Li¹, Xiangyu Kong¹, Qin Zhang¹, Hong Wang¹, Xiaoman Sun¹, Jinsong Li¹, Lili Li¹, Dandi Li¹, Lili Pang¹, Xuancheng Lu², Zhaojun Duan⁴

Affiliations

¹ National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
² National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), Chinese Center for Disease Control and Prevention, Beijing, China.
³ The First Clinical Medical Institute, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
⁴ National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. zhaojund@126.com.

^# Contributed equally.

PMID: 40651980
DOI: 10.1038/s41541-025-01205-x

Abstract

Respiratory syncytial virus (RSV) causes severe respiratory disease in infants and the elderly. However, natural infection fails to induce durable immune protection, and existing mRNA vaccines for older adults exhibit limited long-term efficacy. We developed an antigen engineering strategy inserting ESCRT/ALIX-binding region (EABR) into truncated RSV prefusion F (PreF) cytoplasmic tails to form enveloped virus-like particles (eVLPs). In murine models, PreF-EABR mRNA vaccines elicited higher, more persistent neutralizing antibodies than conventional PreF mRNA, correlating with enhanced germinal center B cell and memory B cell responses. A lower dose of PreF-EABR mRNA (1 μg) suppressed viral load and pathology comparable to higher-dose PreF mRNA (2.5 μg). Transcriptomic analysis showed PreF-EABR mRNA activated toll-like receptor and chemokine signaling pathways, enhancing antibody longevity via platelet-associated signatures. This study explores the development and possible mechanism of long-lasting RSV mRNA vaccines by eVLPs technology, which also suggest its potential application in other vaccines.

Abstract

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