A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus
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 ba...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56302-1 |
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| _version_ | 1823861779126550528 |
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| author | Min Lin Yifan Yin Xiaomeng Zhao Chen Wang Xueqing Zhu Letao Zhan Li Chen Siling Wang Xue Lin Jun Zhang Ningshao Xia Zizheng Zheng |
| author_facet | Min Lin Yifan Yin Xiaomeng Zhao Chen Wang Xueqing Zhu Letao Zhan Li Chen Siling Wang Xue Lin Jun Zhang Ningshao Xia Zizheng Zheng |
| author_sort | Min Lin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-09fb92b7136d4a6db14db3bcc1a84b67 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-09fb92b7136d4a6db14db3bcc1a84b672025-02-09T12:45:10ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-56302-1A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virusMin Lin0Yifan Yin1Xiaomeng Zhao2Chen Wang3Xueqing Zhu4Letao Zhan5Li Chen6Siling Wang7Xue Lin8Jun Zhang9Ningshao Xia10Zizheng Zheng11State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56302-1 |
| spellingShingle | Min Lin Yifan Yin Xiaomeng Zhao Chen Wang Xueqing Zhu Letao Zhan Li Chen Siling Wang Xue Lin Jun Zhang Ningshao Xia Zizheng Zheng A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus Nature Communications |
| title | A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus |
| title_full | A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus |
| title_fullStr | A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus |
| title_full_unstemmed | A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus |
| title_short | A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus |
| title_sort | truncated pre f protein mrna vaccine elicits an enhanced immune response and protection against respiratory syncytial virus |
| url | https://doi.org/10.1038/s41467-025-56302-1 |
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