JCI Insight (Mar 2021)

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

  • Lotfi Chouchane,
  • Jean-Charles Grivel,
  • Elmoubasher Abu Baker Abd Farag,
  • Igor Pavlovski,
  • Selma Maacha,
  • Abbirami Sathappan,
  • Hamad Eid Al-Romaihi,
  • Sirin W.J. Abuaqel,
  • Manar Mahmoud Ahmad Ata,
  • Aouatef Ismail Chouchane,
  • Sami Remadi,
  • Najeeb Halabi,
  • Arash Rafii,
  • Mohammed H. Al-Thani,
  • Nico Marr,
  • Murugan Subramanian,
  • Jingxuan Shan

Journal volume & issue
Vol. 6, no. 5

Abstract

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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.

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