A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity
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Author
de Campos-Mata, Leire
Trinité, Benjamin
Modrego, Andrea
Tejedor Vaquero, Sonia
Pradenas, Edwards
Pons-Grífols, Anna
Rodrigo Melero, Natalia
Carlero, Diego
Marfil, Silvia
Santiago, César
Raïch-Regué, Dàlia
Bueno-Carrasco, María Teresa
Abancó, Ferran
Urrea, Victor
Izquierdo-Useros, Nuria
Riveira-Muñoz, Eva
Ballana, Ester
Carolis, Carlo
Arranz, Rocío
Blanco, Julià
Magri, Giuliana
Publication date
2024-02-05ISSN
2041-1723
Abstract
Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing
human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20
antibody, derived from a receptor binding domain (RBD)-specific IgA+ memory
B cell, with a broad neutralizing activity against former and new SARS-CoV-2
variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently,
17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in “up” position
and blocks the receptor binding motif, as other structurally similar antibodies
do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity
against all variants tested, probably due to a larger RBD contact area. These
results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future
clinical interventions.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
13
Publisher
Nature Research
Is part of
Nature Communications
Citation
De Campos-Mata, Leire, Benjamín Trinité, Andrea Modrego, Sonia Tejedor Vaquero, Edwards Pradenas, Anna Pons-Grífols, Natalia Rodrigo, et al. 2024. “A Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity.” Nature Communications. 15 (1): 1051. doi:10.1038/s41467-024-45171-9.
Program
Sanitat Animal
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- ARTICLES CIENTÍFICS [2555]
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