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ResearchIn-Press PreviewCOVID-19 Open Access | 10.1172/jci.insight.145785

Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2

Lotfi Chouchane,1 Jean-Charles Grivel,2 Elmoubasher Farag,3 Igor Pavlovski,2 Selma Maacha,2 Abbirami Sathappan,2 Hamad Al-Romaihi,3 Sirin Abuaqel,1 Manar Ata,4 Aouatef Ismail Chouchane,4 Sami Remadi,5 Najeeb M. Halabi,6 Arash Rafii,7 Mohammed Al-Thani,8 Nico Marr,4 Murugan Subramanian,1 and Jingxuan Shan7

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Chouchane, L. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Grivel, J. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Farag, E. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Pavlovski, I. in: JCI | PubMed | Google Scholar |

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Maacha, S. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Sathappan, A. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Al-Romaihi, H. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Abuaqel, S. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Ata, M. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Ismail Chouchane, A. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Remadi, S. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Halabi, N. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Rafii, A. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Al-Thani, M. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Marr, N. in: JCI | PubMed | Google Scholar |

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Subramanian, M. in: JCI | PubMed | Google Scholar |

1Department of Microbiology and Immunology, Weill Cornell Medicine, New York City, United States of America

2Deep Phenotyping Core, Sidra Medicine, Doha, Qatar

3Department of Communicable Diseases Control, Ministry of Public Health, Doha, Qatar

4Department of Immunology, Sidra Medicine, Doha, Qatar

5Laboratoire CYTOPATH, Cytopath, Sousse, Tunisia

6Department of Genetic Medicine, Weill Cornell Medicine, New York City, United States of America

7Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar

8Ministry of Public Health, Ministry of Public Health, Doha, Qatar

Find articles by Shan, J. in: JCI | PubMed | Google Scholar |

Published February 2, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.145785.
Copyright © 2021, Chouchane et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 2, 2021 - Version history
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Abstract

The development of prophylactic and therapeutic agents for coronavirus disease 2019 (COVID-19) is a current global health priority. Here, we investigated the presence of cross-neutralizing antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in dromedary camels that were Middle East respiratory syndrome (MERS)-CoV-seropositive but MERS-CoV-free. The tested 229 dromedaries had anti-MERS-CoV camel antibodies with variable cross-reactivity patterns against SARS-CoV-2 proteins, including the S trimer, M, N, and E proteins. Using SARS-CoV-2 competitive immunofluorescence immunoassays and pseudovirus neutralization assays, we found medium-to-high titers of cross-neutralizing antibodies against SARS-CoV-2 in these animals. Through linear B cell epitope mapping using phage immunoprecipitation sequencing and a SARS-CoV-2 peptide/proteome microarray, we identified a large repertoire of betacoronavirus cross-reactive antibody specificities in these dromedaries and demonstrated that the SARS-CoV-2-specific VHH antibody repertoire is qualitatively diverse. This analysis revealed not only several SARS-CoV-2 epitopes that are highly immunogenic in humans, including a neutralizing epitope, but also epitopes exclusively targeted by camel antibodies. The identified SARS-CoV-2 cross-neutralizing camel antibodies are not proposed as a potential treatment for COVID-19. Rather, their presence in non-immunized camels supports the development of SARS-CoV-2 hyperimmune camels, which could be a prominent source of therapeutic agents for the prevention and treatment of COVID-19.

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