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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月5日

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  • Min Lin,
  • Yifan Yin,
  • Xiaomeng Zhao,
  • Chen Wang,
  • Xueqing Zhu,
  • Letao Zhan,
  • Li Chen,
  • Siling Wang,
  • Xue Lin,
  • Jun Zhang,
  • Ningshao Xia,
  • Zizheng Zheng

摘要

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.