tetano
Editor, Senior Moderator
JCI Insight
. 2021 Feb 2;145785.
doi: 10.1172/jci.insight.145785. Online ahead of print.
Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2
Lotfi Chouchane[SUP] 1 [/SUP], Jean-Charles Grivel[SUP] 2 [/SUP], Elmoubasher Farag[SUP] 3 [/SUP], Igor Pavlovski[SUP] 2 [/SUP], Selma Maacha[SUP] 2 [/SUP], Abbirami Sathappan[SUP] 2 [/SUP], Hamad Al-Romaihi[SUP] 3 [/SUP], Sirin Abuaqel[SUP] 1 [/SUP], Manar Ata[SUP] 4 [/SUP], Aouatef Ismail Chouchane[SUP] 4 [/SUP], Sami Remadi[SUP] 5 [/SUP], Najeeb M Halabi[SUP] 6 [/SUP], Arash Rafii[SUP] 7 [/SUP], Mohammed Al-Thani[SUP] 8 [/SUP], Nico Marr[SUP] 4 [/SUP], Murugan Subramanian[SUP] 1 [/SUP], Jingxuan Shan[SUP] 7 [/SUP]
Affiliations
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.
Keywords: Antigen; COVID-19; Immunotherapy; Peptides.
. 2021 Feb 2;145785.
doi: 10.1172/jci.insight.145785. Online ahead of print.
Dromedary camels as a natural source of neutralizing nanobodies against SARS-CoV-2
Lotfi Chouchane[SUP] 1 [/SUP], Jean-Charles Grivel[SUP] 2 [/SUP], Elmoubasher Farag[SUP] 3 [/SUP], Igor Pavlovski[SUP] 2 [/SUP], Selma Maacha[SUP] 2 [/SUP], Abbirami Sathappan[SUP] 2 [/SUP], Hamad Al-Romaihi[SUP] 3 [/SUP], Sirin Abuaqel[SUP] 1 [/SUP], Manar Ata[SUP] 4 [/SUP], Aouatef Ismail Chouchane[SUP] 4 [/SUP], Sami Remadi[SUP] 5 [/SUP], Najeeb M Halabi[SUP] 6 [/SUP], Arash Rafii[SUP] 7 [/SUP], Mohammed Al-Thani[SUP] 8 [/SUP], Nico Marr[SUP] 4 [/SUP], Murugan Subramanian[SUP] 1 [/SUP], Jingxuan Shan[SUP] 7 [/SUP]
Affiliations
- PMID: 33529170
- DOI: 10.1172/jci.insight.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 (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.
Keywords: Antigen; COVID-19; Immunotherapy; Peptides.