A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus

Min Lin, Yifan Yin, Xiaomeng Zhao, Chen Wang, Xueqing Zhu, Letao Zhan, Li Chen, Siling Wang, Xue Lin, Jun Zhang (zhangj@xmu.edu.cn), Ningshao Xia (nsxia@xmu.edu.cn) and Zizheng Zheng (zhengzizheng@xmu.edu.cn)
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Min Lin: Xiamen University
Yifan Yin: Xiamen University
Xiaomeng Zhao: Xiamen University
Chen Wang: Xiamen University
Xueqing Zhu: Xiamen University
Letao Zhan: Xiamen University
Li Chen: Xiamen University
Siling Wang: Xiamen University
Xue Lin: Xiamen University
Jun Zhang: Xiamen University
Ningshao Xia: Xiamen University
Zizheng Zheng: Xiamen University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The Food and Drug Administration (FDA) has approved vaccines designed by GSK, Pfizer and Moderna to protect high-risk populations against respiratory syncytial virus (RSV). These vaccines employ the pre-fusion F (pre-F) protein as the immunogen. In this study, we explored an mRNA vaccine based on a modified pre-F protein called LC2DM-lipid nanoparticle (LC2DM-LNP). This vaccine features a truncated version of the pre-F protein that is anchored to the cell membrane. Our experiments in young and old female mice revealed that the LC2DM-LNP vaccine elicited robust neutralizing antibody titers. Moreover, LC2DM-LNP prompted a Th1-skewed T-cell immune response in female rodent models. Female cotton rats immunized with LC2DM-LNP demonstrated strong immunity to RSV, without signs of vaccine-enhanced respiratory disease (VERD), even in cases of breakthrough infection. Importantly, when administered to pregnant female cotton rats, LC2DM-LNP ensured the transfer of pre-F-specific antibodies to the offspring and provided protection against RSV without increasing lung inflammation. Our findings suggest that LC2DM-LNP could serve as an alternative RSV vaccine candidate for high-risk groups.

Date: 2025
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DOI: 10.1038/s41467-025-56302-1

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