Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection

• DOI: 10.1126/sciadv.aas9667
• Publication Date: 2018-08-08T19:25:10Z
• Authors: V. Stalin Raj; Nisreen M. A. Okba; Javier Gutierrez-...; Dubravka Drabek; Brenda van Dieren; W. Widagdo; Mart M. Lamers; Ivy Widjaja; Raul Fernandez-De...; Isabel Sola; Albert Bensaid; Marion P. Koopmans; Joaquim Segalés; Albert D. M. E. O...; Berend Jan Bosch; Luis Enjuanes; Bart L. Haagmans
• Keywords: Single-domain antibody

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause outbreaks in humans as a result of spillover events from dromedaries. In contrast humans, MERS-CoV-exposed dromedaries develop only very mild infections and exceptionally potent virus-neutralizing antibody responses. These strong responses may be caused by affinity maturation repeated exposure the virus or fact that dromedaries-apart conventional antibodies-have relatively unique, heavy chain-only antibodies (HCAbs). HCAbs are devoid light chains have long complementarity-determining regions with unique epitope binding properties, allowing them recognize bind high epitopes not recognized antibodies. Through direct cloning expression variable (VHHs) bone marrow MERS-CoV-infected dromedaries, we identified several MERS-CoV-specific VHHs nanobodies. vitro, these efficiently blocked entry at picomolar concentrations. The selected receptor domain viral spike protein. Furthermore, camel/human chimeric HCAbs-composed camel VHH linked human Fc lacking CH1 exon-had an extended half-life serum protected mice against lethal MERS-CoV challenge. represent promising alternative strategy novel interventions for but also other emerging pathogens.