IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-56302-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-56302-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-56302-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Lingshu Wang & Wei Shi & M. Gordon Joyce & Kayvon Modjarrad & Yi Zhang & Kwanyee Leung & Christopher R. Lees & Tongqing Zhou & Hadi M. Yassine & Masaru Kanekiyo & Zhi-yong Yang & Xuejun Chen & Michell, 2015. "Evaluation of candidate vaccine approaches for MERS-CoV," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    2. Norbert Pardi & Michael J. Hogan & Rebecca S. Pelc & Hiromi Muramatsu & Hanne Andersen & Christina R. DeMaso & Kimberly A. Dowd & Laura L. Sutherland & Richard M. Scearce & Robert Parks & Wendeline Wa, 2017. "Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination," Nature, Nature, vol. 543(7644), pages 248-251, March.
    3. Anders Krarup & Daphné Truan & Polina Furmanova-Hollenstein & Lies Bogaert & Pascale Bouchier & Ilona J. M. Bisschop & Myra N. Widjojoatmodjo & Roland Zahn & Hanneke Schuitemaker & Jason S. McLellan &, 2015. "A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Aneesh Vijayan & Ronald Vogels & Rachel Groppo & Yi Jin & Selina Khan & Mirjam Kampen & Sytze Jorritsma & Satish Boedhoe & Miranda Baert & Harry Diepen & Harmjan Kuipers & Jan Serroyen & Jorge Reyes- , 2024. "A self-amplifying RNA RSV prefusion-F vaccine elicits potent immunity in pre-exposed and naïve non-human primates," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Yi-Zong Lee & Jerome Han & Yi-Nan Zhang & Garrett Ward & Keegan Braz Gomes & Sarah Auclair & Robyn L. Stanfield & Linling He & Ian A. Wilson & Jiang Zhu, 2024. "Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    3. Momei Zhou & Benjamin Vollmer & Emily Machala & Muyuan Chen & Kay Grünewald & Ann M. Arvin & Wah Chiu & Stefan L. Oliver, 2023. "Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Johannes P. M. Langedijk & Freek Cox & Nicole V. Johnson & Daan Overveld & Lam Le & Ward Hoogen & Richard Voorzaat & Roland Zahn & Leslie Fits & Jarek Juraszek & Jason S. McLellan & Mark J. G. Bakkers, 2024. "Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Xiao Xiao & Arthur Fridman & Lu Zhang & Pavlo Pristatsky & Eberhard Durr & Michael Minnier & Aimin Tang & Kara S. Cox & Zhiyun Wen & Renee Moore & Dongrui Tian & Jennifer D. Galli & Scott Cosmi & Mich, 2022. "Profiling of hMPV F-specific antibodies isolated from human memory B cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Ruipeng Lei & Timothy J. C. Tan & Andrea Hernandez Garcia & Yiquan Wang & Meghan Diefenbacher & Chuyun Teo & Gopika Gopan & Zahra Tavakoli Dargani & Qi Wen Teo & Claire S. Graham & Christopher B. Broo, 2022. "Prevalence and mechanisms of evolutionary contingency in human influenza H3N2 neuraminidase," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Anahita Fathi & Christine Dahlke & Verena Krähling & Alexandra Kupke & Nisreen M. A. Okba & Matthijs P. Raadsen & Jasmin Heidepriem & Marcel A. Müller & Grigori Paris & Susan Lassen & Michael Klüver &, 2022. "Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Mark J. G. Bakkers & Tina Ritschel & Machteld Tiemessen & Jacobus Dijkman & Angelo A. Zuffianò & Xiaodi Yu & Daan Overveld & Lam Le & Richard Voorzaat & Marlies M. Haaren & Martijn Man & Sem Tamara & , 2024. "Efficacious human metapneumovirus vaccine based on AI-guided engineering of a closed prefusion trimer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Nicole V. Johnson & Revina C. Scherpenzeel & Mark J. G. Bakkers & Ajit R. Ramamohan & Daan Overveld & Lam Le & Johannes P. M. Langedijk & Joost A. Kolkman & Jason S. McLellan, 2024. "Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Karen J. Gonzalez & Jiachen Huang & Miria F. Criado & Avik Banerjee & Stephen M. Tompkins & Jarrod J. Mousa & Eva-Maria Strauch, 2024. "A general computational design strategy for stabilizing viral class I fusion proteins," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Ching-Lin Hsieh & Scott A. Rush & Concepcion Palomo & Chia-Wei Chou & Whitney Pickens & Vicente Más & Jason S. McLellan, 2022. "Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    12. Sonal V. Gidwani & Devarshi Brahmbhatt & Aaron Zomback & Mamie Bassie & Jennifer Martinez & Jian Zhuang & John Schulze & Jason S. McLellan & Roberto Mariani & Peter Alff & Daniela Frasca & Bonnie B. B, 2024. "Engineered dityrosine-bonding of the RSV prefusion F protein imparts stability and potency advantages," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    13. Kwinten Sliepen & Laura Radić & Joan Capella-Pujol & Yasunori Watanabe & Ian Zon & Ana Chumbe & Wen-Hsin Lee & Marlon Gast & Jelle Koopsen & Sylvie Koekkoek & Iván Moral-Sánchez & Philip J. M. Brouwer, 2022. "Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56302-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.