Abstract
As the COVID-19 pandemic escalates, the need for effective vaccination programs, diagnosis tools and therapeutic intervention ever increases. Neutralizing binding molecules have become important tools for acute treatment of COVID-19 and also provide a unique possibility to monitor the emergence and presence of a neutralizing immune response in infected or vaccinated individuals. Here we identified 11 unique nanobodies (Nbs) with high binding affinities to the SARS-CoV-2 spike receptor domain (RBD). Of these, 8 effectively block the RBD:ACE2 interface. Via competitive binding analysis and detailed epitope mapping, we grouped all Nbs into 3 sets and demonstrated their neutralizing effect. Combinations from different sets showed a profound synergistic effect by simultaneously targeting different epitopes within the RBD. Finally, we established a competitive multiplex binding assay (“NeutrobodyPlex”) enabling the detection of neutralizing antibodies in serum of infected patients. Overall, our Nbs have high potential for prophylactic and therapeutic options and provide a novel approach to screen for a neutralizing immune response in infected or vaccinated individuals, helping to monitor immune status or guide vaccine design.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
With Alex Dulovic an additional author was added. Gerade Krause has resigned from the authorship. The text was shortend for better understanding and the Supplementary Information are now available as seperate file.