Until now, the majority of anti-SARS-CoV-2 antibody discovery efforts have relied on screening B cells of patients in the convalescent phase.
Here, we describe deep-mining of the antibody repertoires of hospitalised COVID-19 patients using a combination of phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralising antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded potent neutralising antibodies with distinct mechanisms of action, including the identification of a novel non-ACE2 receptor blocking antibody that is not expected to be affected by any of the major viral variants reported.
[Animation: Structure of the SARS-CoV-2 spike protein receptor-binding domain in complex with two antiviral antibody antigen-binding fragments; ACE2 blocking ION_360 (in orange) bound at the canonical ACE2 binding site, and non-ACE2 blocking ION_300 (in green) bound at a distinct epitope.]
The study also highlights the presence of potent neutralising antibodies with near germline sequences within both the IgG and IgM pools at early stages of infection.
Collaborators: IONTAS Ltd, Alchemab Therapeutics Ltd, NIBSC, LifeArc, Abcam, BARTS and London school of medicine, and University of Leicester
FairJourney Biologics is a leading biologics CRO, providing integrated services across antibody discovery, engineering and production to global biopharma. The Company’s significant expertise in phage display technology, combined with a diverse approach to generating both immune and naïve antibody libraries have contributed to a market leading 99%+ project success rate.