Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2
Lotfi Chouchane, … , Murugan Subramanian, Jingxuan Shan
Lotfi Chouchane, … , Murugan Subramanian, Jingxuan Shan
Published February 2, 2021
Citation Information: JCI Insight. 2021;6(5):e145785. https://doi.org/10.1172/jci.insight.145785.
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Research Article COVID-19

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

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.

Authors

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

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Figure 5

Identification of SARS-CoV-2 peptide– and protein-specific antibodies by SARS-CoV-2 peptide/proteome array.

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Identification of SARS-CoV-2 peptide– and protein-specific antibodies by...
Enriched hits SARS-CoV-2–specific (A) total IgG and (B) heavy-chain only IgG and VHH profiles of 56 camel sera. Each square indicates the camel serum (columns) reactivity to the peptides and proteins (rows) of SARS-CoV-2. Mean fluorescence intensity (MFI) is shown by a color gradient scale. (C) SARS-CoV-2 S1/S2 linear epitopes recognized by camel VHH antibodies. In the VirScan column, “+” indicates that the sequence is homologous with SARS-CoV and/or MERS-CoV VirScan hits. NTD, N-terminal domain; RBD, receptor-binding domain; RBM, receptor-binding motif; CTD, C-terminal domain; UD, undefined; HR1, heptad repeat 1. Epitopes found highly immunogenic in humans are highlighted in yellow. The S1-97 peptide, found as a neutralizing epitope in humans, is highlighted in green. (D) The comparison of levels (mean with interquartile range) of shared hits by total IgG (red) and VHH (green) antibodies among 56 camel sera using Student’s t test. *P < 0.05. (E) Selected S1 hits, which were revealed by both anti-total IgG and anti-VHH antibodies, on a structure of S trimer of SARS-CoV-2.