IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45404-x.html
   My bibliography  Save this article

Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge

Author

Listed:
  • Ching-Lin Hsieh

    (The University of Texas at Austin)

  • Sarah R. Leist

    (University of North Carolina at Chapel Hill)

  • Emily Happy Miller

    (Albert Einstein College of Medicine
    Department of Medicine-Infectious Diseases, Albert Einstein College of Medicine)

  • Ling Zhou

    (The University of Texas at Austin)

  • John M. Powers

    (University of North Carolina at Chapel Hill)

  • Alexandra L. Tse

    (Albert Einstein College of Medicine)

  • Albert Wang

    (Albert Einstein College of Medicine)

  • Ande West

    (University of North Carolina at Chapel Hill)

  • Mark R. Zweigart

    (University of North Carolina at Chapel Hill)

  • Jonathan C. Schisler

    (The University of North Carolina at Chapel Hill)

  • Rohit K. Jangra

    (Albert Einstein College of Medicine
    Louisiana State University Health Sciences Center-Shreveport)

  • Kartik Chandran

    (Albert Einstein College of Medicine)

  • Ralph S. Baric

    (University of North Carolina at Chapel Hill)

  • Jason S. McLellan

    (The University of Texas at Austin)

Abstract

Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.

Suggested Citation

  • Ching-Lin Hsieh & Sarah R. Leist & Emily Happy Miller & Ling Zhou & John M. Powers & Alexandra L. Tse & Albert Wang & Ande West & Mark R. Zweigart & Jonathan C. Schisler & Rohit K. Jangra & Kartik Cha, 2024. "Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45404-x
    DOI: 10.1038/s41467-024-45404-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45404-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45404-x?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. Aleksandar Antanasijevic & Leigh M. Sewall & Christopher A. Cottrell & Diane G. Carnathan & Luis E. Jimenez & Julia T. Ngo & Jennifer B. Silverman & Bettina Groschel & Erik Georgeson & Jinal Bhiman & , 2021. "Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. 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.
    3. Mathieu Claireaux & Tom G. Caniels & Marlon Gast & Julianna Han & Denise Guerra & Gius Kerster & Barbera D. C. Schaik & Aldo Jongejan & Angela I. Schriek & Marloes Grobben & Philip J. M. Brouwer & Kar, 2022. "A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Davide F. Robbiani & Christian Gaebler & Frauke Muecksch & Julio C. C. Lorenzi & Zijun Wang & Alice Cho & Marianna Agudelo & Christopher O. Barnes & Anna Gazumyan & Shlomo Finkin & Thomas Hägglöf & Th, 2020. "Convergent antibody responses to SARS-CoV-2 in convalescent individuals," Nature, Nature, vol. 584(7821), pages 437-442, August.
    5. Chunyan Wang & Rien Haperen & Javier Gutiérrez-Álvarez & Wentao Li & Nisreen M. A. Okba & Irina Albulescu & Ivy Widjaja & Brenda Dieren & Raul Fernandez-Delgado & Isabel Sola & Daniel L. Hurdiss & Ola, 2021. "A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    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. Mark Chernyshev & Mrunal Sakharkar & Ruth I. Connor & Haley L. Dugan & Daniel J. Sheward & C. G. Rappazzo & Aron Stålmarck & Mattias N. E. Forsell & Peter F. Wright & Martin Corcoran & Ben Murrell & L, 2023. "Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Timothy J. C. Tan & Zongjun Mou & Ruipeng Lei & Wenhao O. Ouyang & Meng Yuan & Ge Song & Raiees Andrabi & Ian A. Wilson & Collin Kieffer & Xinghong Dai & Kenneth A. Matreyek & Nicholas C. Wu, 2023. "High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Haisheng Yu & Banghui Liu & Yudi Zhang & Xijie Gao & Qian Wang & Haitao Xiang & Xiaofang Peng & Caixia Xie & Yaping Wang & Peiyu Hu & Jingrong Shi & Quan Shi & Pingqian Zheng & Chengqian Feng & Guofan, 2023. "Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Kevin J. Kramer & Erin M. Wilfong & Kelsey Voss & Sierra M. Barone & Andrea R. Shiakolas & Nagarajan Raju & Caroline E. Roe & Naveenchandra Suryadevara & Lauren M. Walker & Steven C. Wall & Ariana Pau, 2022. "Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    5. X. Tong & R. P. McNamara & M. J. Avendaño & E. F. Serrano & T. García-Salum & C. Pardo-Roa & H. L. Bertera & T. M. Chicz & J. Levican & E. Poblete & E. Salinas & A. Muñoz & A. Riquelme & G. Alter & R., 2023. "Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Leire Campos-Mata & Benjamin Trinité & Andrea Modrego & Sonia Tejedor Vaquero & Edwards Pradenas & Anna Pons-Grífols & Natalia Rodrigo Melero & Diego Carlero & Silvia Marfil & César Santiago & Dàlia R, 2024. "A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. A. Brenda Kapingidza & Daniel J. Marston & Caitlin Harris & Daniel Wrapp & Kaitlyn Winters & Dieter Mielke & Lu Xiaozhi & Qi Yin & Andrew Foulger & Rob Parks & Maggie Barr & Amanda Newman & Alexandra , 2023. "Engineered immunogens to elicit antibodies against conserved coronavirus epitopes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Tingting Li & Xiaojian Han & Chenjian Gu & Hangtian Guo & Huajun Zhang & Yingming Wang & Chao Hu & Kai Wang & Fengjiang Liu & Feiyang Luo & Yanan Zhang & Jie Hu & Wang Wang & Shenglong Li & Yanan Hao , 2021. "Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    9. Nathan Post & Danielle Eddy & Catherine Huntley & May C I van Schalkwyk & Madhumita Shrotri & David Leeman & Samuel Rigby & Sarah V Williams & William H Bermingham & Paul Kellam & John Maher & Adrian , 2020. "Antibody response to SARS-CoV-2 infection in humans: A systematic review," PLOS ONE, Public Library of Science, vol. 15(12), pages 1-27, December.
    10. Yi-Nan Zhang & Jennifer Paynter & Aleksandar Antanasijevic & Joel D. Allen & Mor Eldad & Yi-Zong Lee & Jeffrey Copps & Maddy L. Newby & Linling He & Deborah Chavez & Pat Frost & Anna Goodroe & John Du, 2023. "Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates," Nature Communications, Nature, vol. 14(1), pages 1-29, December.
    11. Andrew P. Hederman & Harini Natarajan & Leo Heyndrickx & Kevin K. Ariën & Joshua A. Wiener & Peter F. Wright & Evan M. Bloch & Aaron A. R. Tobian & Andrew D. Redd & Joel N. Blankson & Amihai Rottenstr, 2023. "SARS-CoV-2 vaccination elicits broad and potent antibody effector functions to variants of concern in vulnerable populations," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    12. 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.
    13. Chengzi I. Kaku & Tyler N. Starr & Panpan Zhou & Haley L. Dugan & Paul Khalifé & Ge Song & Elizabeth R. Champney & Daniel W. Mielcarz & James C. Geoghegan & Dennis R. Burton & Raiees Andrabi & Jesse D, 2023. "Evolution of antibody immunity following Omicron BA.1 breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    14. David Chmielewski & Eric A. Wilson & Grigore Pintilie & Peng Zhao & Muyuan Chen & Michael F. Schmid & Graham Simmons & Lance Wells & Jing Jin & Abhishek Singharoy & Wah Chiu, 2023. "Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. Romain Rouet & Jake Y. Henry & Matt D. Johansen & Meghna Sobti & Harikrishnan Balachandran & David B. Langley & Gregory J. Walker & Helen Lenthall & Jennifer Jackson & Stephanie Ubiparipovic & Ohan Ma, 2023. "Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    16. 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.
    17. Chunyan Wang & Emma L. Hesketh & Tatiana M. Shamorkina & Wentao Li & Peter J. Franken & Dubravka Drabek & Rien Haperen & Sarah Townend & Frank J. M. Kuppeveld & Frank Grosveld & Neil A. Ranson & Joost, 2022. "Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    18. Hanna Renk & Alex Dulovic & Alina Seidel & Matthias Becker & Dorit Fabricius & Maria Zernickel & Daniel Junker & Rüdiger Groß & Janis Müller & Alexander Hilger & Sebastian F. N. Bode & Linus Fritsch &, 2022. "Robust and durable serological response following pediatric SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    19. Kuan-Ying A. Huang & Xiaorui Chen & Arpita Mohapatra & Hong Thuy Vy Nguyen & Lisa Schimanski & Tiong Kit Tan & Pramila Rijal & Susan K. Vester & Rory A. Hills & Mark Howarth & Jennifer R. Keeffe & Ale, 2023. "Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    20. Joan Capella-Pujol & Marlon Gast & Laura Radić & Ian Zon & Ana Chumbe & Sylvie Koekkoek & Wouter Olijhoek & Janke Schinkel & Marit J. Gils & Rogier W. Sanders & Kwinten Sliepen, 2023. "Signatures of VH1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins," Nature Communications, Nature, vol. 14(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:15:y:2024:i:1:d:10.1038_s41467-024-45404-x. 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.