A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity

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...

Descripción completa

Detalles Bibliográficos
Autores: Campos Mata, Leire de, Trinité, Benjamin, Modrego Guillén, Andrea, Tejedor Vaquero, Sonia, Pradenas Saavedra, Edwards, Pons Grífols, Anna, Rodrigo Melero, Natalia, Carlero, Diego, Marfil, Silvia, Santiago, César, Raïch Regué, Dàlia, Bueno Carrasco, María Teresa, Tarrés Freixas, Ferran, Abancó, Ferran, Urrea, Victor, Izquierdo Useros, Nuria, Riveira Muñoz, Eva, Ballana, Ester, Pérez Maillo, Mónica, Vergara Alert, Júlia, Segalés, Joaquim, Carolis, Carlo, Arranz, Rocío, Blanco, Julià, Magri, Giuliana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/223222
Acceso en línea:https://hdl.handle.net/2445/223222
Access Level:acceso abierto
Palabra clave:COVID-19
Anticossos monoclonals
Glicoproteïnes
SARS-CoV-2
Monoclonal antibodies
Glycoproteins
Descripción
Sumario: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.

Similares en LA Referencia