@article{10.1172/jci.insight.145785, author = {Lotfi Chouchane AND Jean-Charles Grivel AND Elmoubasher Abu Baker Abd Farag AND Igor Pavlovski AND Selma Maacha AND Abbirami Sathappan AND Hamad Eid Al-Romaihi AND Sirin W.J. Abuaqel AND Manar Mahmoud Ahmad Ata AND Aouatef Ismail Chouchane AND Sami Remadi AND Najeeb Halabi AND Arash Rafii AND Mohammed H. Al-Thani AND Nico Marr AND Murugan Subramanian AND Jingxuan Shan}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2}, year = {2021}, month = {3}, volume = {6}, url = {https://insight.jci.org/articles/view/145785}, 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 coronavirus (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 and 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 nonimmunized 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.}, number = {5}, doi = {10.1172/jci.insight.145785}, url = {https://doi.org/10.1172/jci.insight.145785}, }