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 2

Seroreactivity of dromedary camels to MERS-CoV S protein and SARS-CoV-2 proteins.

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Seroreactivity of dromedary camels to MERS-CoV S protein and SARS-CoV-2 ...
(A) Antibody-binding activities of 229 dromedary sera diluted at 1:20. The asterisks represent serological negative samples that are below 2 times the value of beads only. Each rectangle indicates the camel serum (rows) reactivity to MERS-CoV S protein and to SARS-CoV-2 proteins (columns). Mean fluorescence intensity (MFI) is shown by a color gradient scale. (B) The seroprevalence and distribution of antibody-binding activities (mean with interquartile range) of 229 serum samples to each protein. The dashed line indicates the baseline, which is 2 times the value of beads only. (C) Schematic structure of IgG1, IgG2/3, and VHH/SdAb. Anti-IgG antibody can recognize total camel IgG antibodies, whereas anti-VHH antibody can only recognize heavy chain alone antibody, IgG2/3, and SdAb. SdAb, single-domain antibody, also known as nanobody. (D) SARS-CoV-2 S trimer binding curves for 12 camel sera revealed by anti-IgG camel antibodies (top) and anti-VHH antibodies (bottom), both of which are conjugated with fluorochrome. The sera were diluted 10 times and then subjected to 7-step, 2-fold series dilutions. Each datum point represents the median of up to 500 individual beads. GAC, goat anti-camel IgG; AFU, arbitrary fluorescence units.