RT Journal Article
SR Electronic
T1 A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.20.524748
DO 10.1101/2023.01.20.524748
A1 Leire de Campos-Mata
A1 Benjamin Trinité
A1 Andrea Modrego
A1 Sonia Tejedor Vaquero
A1 Edwards Pradenas
A1 Natalia Rodrigo Melero
A1 Diego Carlero
A1 Silvia Marfil
A1 Anna Pons-Grífols
A1 María Teresa Bueno-Carrasco
A1 César Santiago
A1 Ferran Tarrés-Freixas
A1 Victor Urrea
A1 Nuria Izquierdo
A1 Eva Riveira-Muñoz
A1 Ester Ballana
A1 Mónica Pérez
A1 Júlia Vergara-Alert
A1 Joaquim Segalés
A1 Carlo Carolis
A1 Rocío Arranz
A1 Julià Blanco
A1 Giuliana Magri
YR 2023
UL http://biorxiv.org/content/early/2023/01/23/2023.01.20.524748.abstract
AB In the present study we report the functional and structural characterization of 17T2, a new highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody (mAb) isolated from a convalescent COVID-19 individual infected during the first wave of the COVID-19 pandemic. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell and developed as a human recombinant IgG1. Functional characterization revealed that 17T2 mAb has a high and exceptionally broad neutralizing activity against all SARS-CoV-2 spike variants tested, including BQ.1.1. Moreover, 17T2 mAb has in vivo prophylactic activity against Omicron BA.1.1 infection in K18-hACE2 transgenic mice. 3D reconstruction from cryogenic-electron microscopy (cryo-EM) showed that 17T2 binds the Omicron BA.1 spike protein with the RBD domains in “up” position and recognizes an epitope overlapping with the receptor binding motif, as it is the case for other structurally similar neutralizing mAbs, including S2E12. Yet, unlike S2E12, 17T2 retained its high neutralizing activity against all Omicron sublineages tested, probably due to a larger contact area with the RBD, which could confer a higher resilience to spike mutations. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 mAb as a potential candidate for future therapeutic and prophylactic interventions.Competing Interest StatementUnrelated to the submitted work, J.B. is founder and shareholder of AlbaJuna Therapeutics, S.L; J.B. reports institutional grants from HIPRA, NESAPOR Europe, and MSD. The authors declare no other competing conflicts of interests. This work is protected by intellectual property rights through the patent EP22382940, published by G.M., S.T.V., L.D.C.-M., C.C., J.B.A., B.T., E.P. (co-authors of this work).