IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41171-3.html
   My bibliography  Save this article

Multifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses

Author

Listed:
  • Nathaniel S. Chapman

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Ruben J. G. Hulswit

    (University of Oxford)

  • Jonna L. B. Westover

    (Utah State University)

  • Robert Stass

    (University of Oxford)

  • Guido C. Paesen

    (University of Oxford)

  • Elad Binshtein

    (Vanderbilt University Medical Center)

  • Joseph X. Reidy

    (Vanderbilt University Medical Center)

  • Taylor B. Engdahl

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Laura S. Handal

    (Vanderbilt University Medical Center)

  • Alejandra Flores

    (Vanderbilt University Medical Center)

  • Brian B. Gowen

    (Utah State University)

  • Thomas A. Bowden

    (University of Oxford)

  • James E. Crowe

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

Abstract

The zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined. Surprisingly, the Gn domain-A antibody does not directly block RVFV Gn interaction with the host receptor low density lipoprotein receptor-related protein 1 (LRP1) as determined by a competitive assay. This study identifies a rationally designed combination of human mAbs deserving of future investigation for use in humans against RVFV infection. Using a two-pronged mechanistic approach, we demonstrate the potent efficacy of a rationally designed combination mAb therapeutic.

Suggested Citation

  • Nathaniel S. Chapman & Ruben J. G. Hulswit & Jonna L. B. Westover & Robert Stass & Guido C. Paesen & Elad Binshtein & Joseph X. Reidy & Taylor B. Engdahl & Laura S. Handal & Alejandra Flores & Brian B, 2023. "Multifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41171-3
    DOI: 10.1038/s41467-023-41171-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41171-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41171-3?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. Steinar Halldorsson & Sai Li & Mengqiu Li & Karl Harlos & Thomas A. Bowden & Juha T. Huiskonen, 2018. "Shielding and activation of a viral membrane fusion protein," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    2. Jennifer N. Rauch & Gabriel Luna & Elmer Guzman & Morgane Audouard & Collin Challis & Youssef E. Sibih & Carolina Leshuk & Israel Hernandez & Susanne Wegmann & Bradley T. Hyman & Viviana Gradinaru & M, 2020. "LRP1 is a master regulator of tau uptake and spread," Nature, Nature, vol. 580(7803), pages 381-385, April.
    3. Seth J. Zost & Pavlo Gilchuk & James Brett Case & Elad Binshtein & Rita E. Chen & Joseph P. Nkolola & Alexandra Schäfer & Joseph X. Reidy & Andrew Trivette & Rachel S. Nargi & Rachel E. Sutton & Navee, 2020. "Potently neutralizing and protective human antibodies against SARS-CoV-2," Nature, Nature, vol. 584(7821), pages 443-449, August.
    4. Benjamin Gutjahr & Markus Keller & Melanie Rissmann & Felicitas von Arnim & Susanne Jäckel & Sven Reiche & Reiner Ulrich & Martin H Groschup & Martin Eiden, 2020. "Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 14(3), pages 1-18, March.
    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. 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.
    2. Wenkai Han & Ningning Chen & Xinzhou Xu & Adil Sahil & Juexiao Zhou & Zhongxiao Li & Huawen Zhong & Elva Gao & Ruochi Zhang & Yu Wang & Shiwei Sun & Peter Pak-Hang Cheung & Xin Gao, 2023. "Predicting the antigenic evolution of SARS-COV-2 with deep learning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Cynthia M. McMillen & Nathaniel S. Chapman & Ryan M. Hoehl & Lauren B. Skvarca & Madeline M. Schwarz & Laura S. Handal & James E. Crowe & Amy L. Hartman, 2023. "A highly potent human neutralizing antibody prevents vertical transmission of Rift Valley fever virus in a rat model," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Ting Lu & Rui Ma & Wenjuan Dong & Kun-Yu Teng & Daniel S. Kollath & Zhiyao Li & Jinhee Yi & Christian Bustillos & Shoubao Ma & Lei Tian & Anthony G. Mansour & Zhenlong Li & Erik W. Settles & Jianying , 2022. "Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Vishruth Mullapudi & Jaime Vaquer-Alicea & Vaibhav Bommareddy & Anthony R. Vega & Bryan D. Ryder & Charles L. White & Marc. I. Diamond & Lukasz A. Joachimiak, 2023. "Network of hotspot interactions cluster tau amyloid folds," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. James Brett Case & Samantha Mackin & John M. Errico & Zhenlu Chong & Emily A. Madden & Bradley Whitener & Barbara Guarino & Michael A. Schmid & Kim Rosenthal & Kuishu Ren & Ha V. Dang & Gyorgy Snell &, 2022. "Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    7. Yanqun Wang & An Yan & Deyong Song & Maoqin Duan & Chuangchuang Dong & Jiantao Chen & Zihe Jiang & Yuanzhu Gao & Muding Rao & Jianxia Feng & Zhaoyong Zhang & Ruxi Qi & Xiaomin Ma & Hong Liu & Beibei Y, 2024. "Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Meihua Jin & Hiroki Shiwaku & Hikari Tanaka & Takayuki Obita & Sakurako Ohuchi & Yuki Yoshioka & Xiaocen Jin & Kanoh Kondo & Kyota Fujita & Hidenori Homma & Kazuyuki Nakajima & Mineyuki Mizuguchi & Hi, 2021. "Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    9. 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.
    10. Emanuele Andreano & Ida Paciello & Giulio Pierleoni & Giuseppe Maccari & Giada Antonelli & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevra Giglioli & Giulia Piccini & Concetta De Santi &, 2023. "mRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    11. Omar Nyabi & Mostafa Bentahir & Jérôme Ambroise & Bertrand Bearzatto & Nawfal Chibani & Benjamin Smits & Jean François Durant & Aleksandr Vybornov & Olivier Thellin & Benaissa El Moualij & Jean-Luc Ga, 2021. "Diagnostic Value of IgM and IgG Detection in COVID-19 Diagnosis by the Mobile Laboratory B-LiFE: A Massive Testing Strategy in the Piedmont Region," IJERPH, MDPI, vol. 18(7), pages 1-10, March.
    12. Lei Peng & Yingxia Hu & Madeleine C. Mankowski & Ping Ren & Rita E. Chen & Jin Wei & Min Zhao & Tongqing Li & Therese Tripler & Lupeng Ye & Ryan D. Chow & Zhenhao Fang & Chunxiang Wu & Matthew B. Dong, 2022. "Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    13. Jiyeon Lee & Julie M. Dimitry & Jong Hee Song & Minsoo Son & Patrick W. Sheehan & Melvin W. King & G. Travis Tabor & Young Ah Goo & Mitchell A. Lazar & Leonard Petrucelli & Erik S. Musiek, 2023. "Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Daniel N. Streblow & Alec J. Hirsch & Jeffrey J. Stanton & Anne D. Lewis & Lois Colgin & Ann J. Hessell & Craig N. Kreklywich & Jessica L. Smith & William F. Sutton & David Chauvin & Jennifer Woo & Be, 2023. "Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. Shouwen Du & Ruchao Peng & Wang Xu & Xiaoyun Qu & Yuhang Wang & Jiamin Wang & Letian Li & Mingyao Tian & Yudong Guan & Jigang Wang & Guoqing Wang & Hao Li & Lingcong Deng & Xiaoshuang Shi & Yidan Ma &, 2023. "Cryo-EM structure of severe fever with thrombocytopenia syndrome virus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Sheng Wang, 2023. "Can Digital Financial Behavior Improve the Effect of Prevention and Control of COVID-19 in China?," Global Journal of Health Science, Canadian Center of Science and Education, vol. 15(5), pages 1-11, May.
    17. Daming Zhou & Piyada Supasa & Chang Liu & Aiste Dijokaite-Guraliuc & Helen M. E. Duyvesteyn & Muneeswaran Selvaraj & Alexander J. Mentzer & Raksha Das & Wanwisa Dejnirattisai & Nigel Temperton & Paul , 2024. "The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Sean Harrington & Jacob Pyche & Andrew R. Burns & Tina Spalholz & Kaetlyn T. Ryan & Rachel J. Baker & Justin Ching & Lucien Rufener & Mark Lautens & Daniel Kulke & Alexandre Vernudachi & Mostafa Zaman, 2023. "Nemacol is a small molecule inhibitor of C. elegans vesicular acetylcholine transporter with anthelmintic potential," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Benjamin Gutjahr & Markus Keller & Melanie Rissmann & Felicitas von Arnim & Susanne Jäckel & Sven Reiche & Reiner Ulrich & Martin H Groschup & Martin Eiden, 2020. "Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 14(3), pages 1-18, March.
    20. Elizabeth M. Parzych & Jianqiu Du & Ali R. Ali & Katherine Schultheis & Drew Frase & Trevor R. F. Smith & Jiayan Cui & Neethu Chokkalingam & Nicholas J. Tursi & Viviane M. Andrade & Bryce M. Warner & , 2022. "DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2," 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:14:y:2023:i:1:d:10.1038_s41467-023-41171-3. 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.