IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v595y2021i7869d10.1038_s41586-021-03673-2.html
   My bibliography  Save this article

Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants

Author

Listed:
  • Zhiqiang Ku

    (The University of Texas Health Science Center at Houston)

  • Xuping Xie

    (University of Texas Medical Branch)

  • Paul R. Hinton

    (IGM Biosciences)

  • Xinli Liu

    (University of Houston)

  • Xiaohua Ye

    (The University of Texas Health Science Center at Houston)

  • Antonio E. Muruato

    (University of Texas Medical Branch
    University of Texas Medical Branch)

  • Dean C. Ng

    (IGM Biosciences)

  • Sujit Biswas

    (University of Houston)

  • Jing Zou

    (University of Texas Medical Branch)

  • Yang Liu

    (University of Texas Medical Branch)

  • Deepal Pandya

    (IGM Biosciences)

  • Vineet D. Menachery

    (University of Texas Medical Branch)

  • Sachi Rahman

    (IGM Biosciences)

  • Yu-An Cao

    (IGM Biosciences)

  • Hui Deng

    (The University of Texas Health Science Center at Houston)

  • Wei Xiong

    (The University of Texas Health Science Center at Houston)

  • Kevin B. Carlin

    (IGM Biosciences)

  • Junquan Liu

    (The University of Texas Health Science Center at Houston)

  • Hang Su

    (The University of Texas Health Science Center at Houston)

  • Elizabeth J. Haanes

    (IGM Biosciences)

  • Bruce A. Keyt

    (IGM Biosciences)

  • Ningyan Zhang

    (The University of Texas Health Science Center at Houston)

  • Stephen F. Carroll

    (IGM Biosciences)

  • Pei-Yong Shi

    (University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch
    University of Texas Medical Branch)

  • Zhiqiang An

    (The University of Texas Health Science Center at Houston)

Abstract

Resistance represents a major challenge for antibody-based therapy for COVID-191–4. Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern—B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)—and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19.

Suggested Citation

  • Zhiqiang Ku & Xuping Xie & Paul R. Hinton & Xinli Liu & Xiaohua Ye & Antonio E. Muruato & Dean C. Ng & Sujit Biswas & Jing Zou & Yang Liu & Deepal Pandya & Vineet D. Menachery & Sachi Rahman & Yu-An C, 2021. "Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants," Nature, Nature, vol. 595(7869), pages 718-723, July.
  • Handle: RePEc:nat:nature:v:595:y:2021:i:7869:d:10.1038_s41586-021-03673-2
    DOI: 10.1038/s41586-021-03673-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03673-2
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-021-03673-2?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Anna R. Mäkelä & Hasan Uğurlu & Liina Hannula & Ravi Kant & Petja Salminen & Riku Fagerlund & Sanna Mäki & Anu Haveri & Tomas Strandin & Lauri Kareinen & Jussi Hepojoki & Suvi Kuivanen & Lev Levanov &, 2023. "Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Zhiqiang Ku & Xuping Xie & Jianqing Lin & Peng Gao & Bin Wu & Abbas El Sahili & Hang Su & Yang Liu & Xiaohua Ye & Eddie Yongjun Tan & Xin Li & Xuejun Fan & Boon Chong Goh & Wei Xiong & Hannah Boyd & A, 2022. "Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Zhenzhen Wang & Shiqi Hu & Kristen D. Popowski & Shuo Liu & Dashuai Zhu & Xuan Mei & Junlang Li & Yilan Hu & Phuong-Uyen C. Dinh & Xiaojie Wang & Ke Cheng, 2024. "Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Juan Liu & Fengfeng Mao & Jianhe Chen & Shuaiyao Lu & Yonghe Qi & Yinyan Sun & Linqiang Fang & Man Lung Yeung & Chunmei Liu & Guimei Yu & Guangyu Li & Ximing Liu & Yuansheng Yao & Panpan Huang & Dongx, 2023. "An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Yang Liu & Xianwen Zhang & Jianying Liu & Hongjie Xia & Jing Zou & Antonio E. Muruato & Sivakumar Periasamy & Chaitanya Kurhade & Jessica A. Plante & Nathen E. Bopp & Birte Kalveram & Alexander Bukrey, 2022. "A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions," Nature Communications, Nature, vol. 13(1), pages 1-14, 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:nature:v:595:y:2021:i:7869:d:10.1038_s41586-021-03673-2. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.