IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33030-4.html
   My bibliography  Save this article

IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern

Author

Listed:
  • Matthew R. Chang

    (Dana-Farber Cancer Institute)

  • Luke Tomasovic

    (Dana-Farber Cancer Institute)

  • Natalia A. Kuzmina

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

  • Adam J. Ronk

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

  • Patrick O. Byrne

    (University of Texas)

  • Rebecca Johnson

    (Boston University, School of Medicine)

  • Nadia Storm

    (Boston University, School of Medicine)

  • Eduardo Olmedillas

    (La Jolla Institute for Immunology)

  • Yixuan J. Hou

    (University of North Carolina at Chapel Hill)

  • Alexandra Schäfer

    (University of North Carolina at Chapel Hill)

  • Sarah R. Leist

    (University of North Carolina at Chapel Hill)

  • Longping V. Tse

    (University of North Carolina at Chapel Hill)

  • Hanzhong Ke

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Christian Coherd

    (Dana-Farber Cancer Institute)

  • Katrina Nguyen

    (Dana-Farber Cancer Institute)

  • Maliwan Kamkaew

    (Dana-Farber Cancer Institute)

  • Anna Honko

    (Boston University, School of Medicine)

  • Quan Zhu

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Galit Alter

    (MIT and Harvard)

  • Erica Ollmann Saphire

    (La Jolla Institute for Immunology)

  • Jason S. McLellan

    (University of Texas)

  • Anthony Griffiths

    (Boston University, School of Medicine)

  • Ralph S. Baric

    (University of North Carolina at Chapel Hill)

  • Alexander Bukreyev

    (University of Texas Medical Branch
    Galveston National Laboratory
    University of Texas Medical Branch)

  • Wayne A. Marasco

    (Dana-Farber Cancer Institute
    Harvard Medical School)

Abstract

Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.

Suggested Citation

  • Matthew R. Chang & Luke Tomasovic & Natalia A. Kuzmina & Adam J. Ronk & Patrick O. Byrne & Rebecca Johnson & Nadia Storm & Eduardo Olmedillas & Yixuan J. Hou & Alexandra Schäfer & Sarah R. Leist & Lon, 2022. "IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33030-4
    DOI: 10.1038/s41467-022-33030-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33030-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-33030-4?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. Kenneth H. Dinnon & Sarah R. Leist & Alexandra Schäfer & Caitlin E. Edwards & David R. Martinez & Stephanie A. Montgomery & Ande West & Boyd L. Yount & Yixuan J. Hou & Lily E. Adams & Kendra L. Gully , 2020. "A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures," Nature, Nature, vol. 586(7830), pages 560-566, October.
    2. M. Alejandra Tortorici & Nadine Czudnochowski & Tyler N. Starr & Roberta Marzi & Alexandra C. Walls & Fabrizia Zatta & John E. Bowen & Stefano Jaconi & Julia Iulio & Zhaoqian Wang & Anna Marco & Saman, 2021. "Broad sarbecovirus neutralization by a human monoclonal antibody," Nature, Nature, vol. 597(7874), pages 103-108, September.
    3. Pengfei Wang & Manoj S. Nair & Lihong Liu & Sho Iketani & Yang Luo & Yicheng Guo & Maple Wang & Jian Yu & Baoshan Zhang & Peter D. Kwong & Barney S. Graham & John R. Mascola & Jennifer Y. Chang & Mich, 2021. "Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7," Nature, Nature, vol. 593(7857), pages 130-135, May.
    4. Delphine Planas & David Veyer & Artem Baidaliuk & Isabelle Staropoli & Florence Guivel-Benhassine & Maaran Michael Rajah & Cyril Planchais & Françoise Porrot & Nicolas Robillard & Julien Puech & Matth, 2021. "Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization," Nature, Nature, vol. 596(7871), pages 276-280, August.
    5. Seiya Ozono & Yanzhao Zhang & Hirotaka Ode & Kaori Sano & Toong Seng Tan & Kazuo Imai & Kazuyasu Miyoshi & Satoshi Kishigami & Takamasa Ueno & Yasumasa Iwatani & Tadaki Suzuki & Kenzo Tokunaga, 2021. "SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    6. Sin Fun Sia & Li-Meng Yan & Alex W. H. Chin & Kevin Fung & Ka-Tim Choy & Alvina Y. L. Wong & Prathanporn Kaewpreedee & Ranawaka A. P. M. Perera & Leo L. M. Poon & John M. Nicholls & Malik Peiris & Hui, 2020. "Pathogenesis and transmission of SARS-CoV-2 in golden hamsters," Nature, Nature, vol. 583(7818), pages 834-838, July.
    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. Yin-Feng Kang & Cong Sun & Jing Sun & Chu Xie & Zhen Zhuang & Hui-Qin Xu & Zheng Liu & Yi-Hao Liu & Sui Peng & Run-Yu Yuan & Jin-Cun Zhao & Mu-Sheng Zeng, 2022. "Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Sapna Sharma & Thomas Vercruysse & Lorena Sanchez-Felipe & Winnie Kerstens & Madina Rasulova & Lindsey Bervoets & Carolien Keyzer & Rana Abdelnabi & Caroline S. Foo & Viktor Lemmens & Dominique Loover, 2022. "Updated vaccine protects against SARS-CoV-2 variants including Omicron (B.1.1.529) and prevents transmission in hamsters," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. de León, Ugo Avila-Ponce & Avila-Vales, Eric & Huang, Kuan-lin, 2022. "Modeling COVID-19 dynamic using a two-strain model with vaccination," Chaos, Solitons & Fractals, Elsevier, vol. 157(C).
    4. Bruno A. Rodriguez-Rodriguez & Grace O. Ciabattoni & Ralf Duerr & Ana M. Valero-Jimenez & Stephen T. Yeung & Keaton M. Crosse & Austin R. Schinlever & Lucie Bernard-Raichon & Joaquin Rodriguez Galvan , 2023. "A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. 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.
    6. Mingxi Li & Yifei Ren & Zhen Qin Aw & Bo Chen & Ziqing Yang & Yuqing Lei & Lin Cheng & Qingtai Liang & Junxian Hong & Yiling Yang & Jing Chen & Yi Hao Wong & Jing Wei & Sisi Shan & Senyan Zhang & Jiwa, 2022. "Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Ryuta Uraki & Shun Iida & Peter J. Halfmann & Seiya Yamayoshi & Yuichiro Hirata & Kiyoko Iwatsuki-Horimoto & Maki Kiso & Mutsumi Ito & Yuri Furusawa & Hiroshi Ueki & Yuko Sakai-Tagawa & Makoto Kuroda , 2023. "Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    8. Kara W. Chew & Carlee Moser & Eric S. Daar & David A. Wohl & Jonathan Z. Li & Robert W. Coombs & Justin Ritz & Mark Giganti & Arzhang Cyrus Javan & Yijia Li & Manish C. Choudhary & Rinki Deo & Carlos , 2022. "Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Guilherme Dias de Melo & Victoire Perraud & Flavio Alvarez & Alba Vieites-Prado & Seonhee Kim & Lauriane Kergoat & Anthony Coleon & Bettina Salome Trüeb & Magali Tichit & Aurèle Piazza & Agnès Thierry, 2023. "Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Elham Khatamzas & Markus H. Antwerpen & Alexandra Rehn & Alexander Graf & Johannes Christian Hellmuth & Alexandra Hollaus & Anne-Wiebe Mohr & Erik Gaitzsch & Tobias Weiglein & Enrico Georgi & Clemens , 2022. "Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Leiping Zeng & Yanxia Liu & Xammy Huu Nguyenla & Timothy R. Abbott & Mengting Han & Yanyu Zhu & Augustine Chemparathy & Xueqiu Lin & Xinyi Chen & Haifeng Wang & Draven A. Rane & Jordan M. Spatz & Sake, 2022. "Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Xiaoqi Yu & Dong Wei & Wenxin Xu & Chuanmiao Liu & Wentian Guo & Xinxin Li & Wei Tan & Leshan Liu & Xinxin Zhang & Jieming Qu & Zhitao Yang & Erzhen Chen, 2022. "Neutralizing activity of BBIBP-CorV vaccine-elicited sera against Beta, Delta and other SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    13. Dennis Lapuente & Jana Fuchs & Jonas Willar & Ana Vieira Antão & Valentina Eberlein & Nadja Uhlig & Leila Issmail & Anna Schmidt & Friederike Oltmanns & Antonia Sophia Peter & Sandra Mueller-Schmucker, 2021. "Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    14. Byung Uk Lee, 2021. "Why Does the SARS-CoV-2 Delta VOC Spread So Rapidly? Universal Conditions for the Rapid Spread of Respiratory Viruses, Minimum Viral Loads for Viral Aerosol Generation, Effects of Vaccination on Viral," IJERPH, MDPI, vol. 18(18), pages 1-6, September.
    15. Haogao Gu & Ahmed Abdul Quadeer & Pavithra Krishnan & Daisy Y. M. Ng & Lydia D. J. Chang & Gigi Y. Z. Liu & Samuel M. S. Cheng & Tommy T. Y. Lam & Malik Peiris & Matthew R. McKay & Leo L. M. Poon, 2023. "Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. 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.
    17. Valentina Marziano & Giorgio Guzzetta & Alessia Mammone & Flavia Riccardo & Piero Poletti & Filippo Trentini & Mattia Manica & Andrea Siddu & Antonino Bella & Paola Stefanelli & Patrizio Pezzotti & Ma, 2021. "The effect of COVID-19 vaccination in Italy and perspectives for living with the virus," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    18. Emanuele Andreano & Ida Paciello & Silvia Marchese & Lorena Donnici & Giulio Pierleoni & Giulia Piccini & Noemi Manganaro & Elisa Pantano & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevr, 2022. "Anatomy of Omicron BA.1 and BA.2 neutralizing antibodies in COVID-19 mRNA vaccinees," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    19. Haofeng Wang & Qi Yang & Xiaoce Liu & Zili Xu & Maolin Shao & Dongxu Li & Yinkai Duan & Jielin Tang & Xianqiang Yu & Yumin Zhang & Aihua Hao & Yajie Wang & Jie Chen & Chenghao Zhu & Luke Guddat & Hong, 2023. "Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Daiki Yamaguchi & Odgerel Chimed-Ochir & Yui Yumiya & Eisaku Kishita & Tomoyuki Akita & Junko Tanaka & Tatsuhiko Kubo, 2024. "Potential Risk Factors to COVID-19 Severity: Comparison of SARS-CoV-2 Delta- and Omicron-Dominant Periods," IJERPH, MDPI, vol. 21(3), pages 1-11, March.

    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:13:y:2022:i:1:d:10.1038_s41467-022-33030-4. 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.