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

Author

Listed:
  • Min Lin

    (Xiamen University
    Xiamen University)

  • Yifan Yin

    (Xiamen University
    Xiamen University)

  • Xiaomeng Zhao

    (Xiamen University
    Xiamen University)

  • Chen Wang

    (Xiamen University
    Xiamen University)

  • Xueqing Zhu

    (Xiamen University
    Xiamen University)

  • Letao Zhan

    (Xiamen University
    Xiamen University)

  • Li Chen

    (Xiamen University
    Xiamen University)

  • Siling Wang

    (Xiamen University
    Xiamen University)

  • Xue Lin

    (Xiamen University
    Xiamen University)

  • Jun Zhang

    (Xiamen University
    Xiamen University)

  • Ningshao Xia

    (Xiamen University
    Xiamen University)

  • Zizheng Zheng

    (Xiamen University
    Xiamen University)

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.

Suggested Citation

  • Min Lin & Yifan Yin & Xiaomeng Zhao & Chen Wang & Xueqing Zhu & Letao Zhan & Li Chen & Siling Wang & Xue Lin & Jun Zhang & Ningshao Xia & Zizheng Zheng, 2025. "A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56302-1
    DOI: 10.1038/s41467-025-56302-1
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