Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells.

TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation. The exceptionally diverse antibodies included RBD-binders with broad neutralizing activity against SARS-CoV-2 variants, and S2-binders with broad specificity against betacoronaviruses and the ability to block membrane fusion. A subset of these RBD- and S2-binding antibodies demonstrated robust protection against challenge in hamster and mouse models. This high-throughput approach can accelerate discovery of diverse, multifunctional antibodies against any target of interest.

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Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests At the time of execution of this work, G.J.K, B.E.R.R., M.E.G., A.J.M., J.T., Y.L., P.E., A.M., J.G., E.E., N.L., R.B., A.C., H.A., T.C., A.D., R.H., C.L., D.P., C.W., J.N.D., L.B., A.S., B.H., M.K., E.Y., H.S.R., S.B., and A.E.G. were employees and held equity in Adaptive Biotechnologies. L.L., J.W., C.L., and L.C. declare employment and equity at GenScript. G.A. is a founder of Seromyx Systems and C.A. declares no conflict of interest. Patent applications relating to SARS COV-2 antibodies are pending.