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

Lotfi Chouchane; Jean-Charles Grivel; Elmoubasher Farag; Igor Pavlovski; Selma Maacha; Abbirami Sathappan; Hamad Al-Romaihi; Sirin Abuaqel; Manar Ata; Aouatef Ismail Chouchane; Sami Remadi; Najeeb M. Halabi; Arash Rafii; Mohammed Al-Thani; Nico Marr; Murugan Subramanian; Jingxuan Shan

doi: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

Published February 2, 2021 - More info

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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.

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

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