A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity
Por:
de Campos-Mata, L, Trinité, B, Modrego, A, Vaquero, ST, Pradenas, E, Pons-Grífols, A, Melero, NR, Carlero, D, Marfil, S, Santiago, C, Raïch-Regué, D, Bueno-Carrasco, MT, Tarrés-Freixas, F, Abancó, F, Urrea, V, Izquierdo-Useros, N, Riveira-Muñoz, E, Ballana, E, Pérez, M, Vergara-Alert, J, Segalés, J, Carolis, C, Arranz, R, Blanco, J and Magri, G
Publicada:
5 feb 2024
Resumen:
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/kappa 3-20 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.
Characterisation of monoclonal antibodies against SARS-CoV-2 are useful for potential therapeutics or to understand more about the immune response to this virus. Here the authors characterise a monoclonal antibody that has a broad range of reactivity against SARS-CoV-2 variants and measure how it binds to its specific target region of the receptor binding domain.
Filiaciones:
de Campos-Mata, L:
Hosp Mar Res Inst IMIM, Translat Clin Res Program, Barcelona, Spain
Karolinska Inst, Dept Med Biochem & Biophys, Div Immunol, Stockholm, Sweden
Trinité, B:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
Modrego, A:
Ctr Nacl Biotecnol CNB CSIC, Madrid, Spain
Vaquero, ST:
Hosp Mar Res Inst IMIM, Translat Clin Res Program, Barcelona, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
Pons-Grífols, A:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
Melero, NR:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain
Carlero, D:
Ctr Nacl Biotecnol CNB CSIC, Madrid, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
Santiago, C:
Ctr Nacl Biotecnol CNB CSIC, Madrid, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
Bueno-Carrasco, MT:
Ctr Nacl Biotecnol CNB CSIC, Madrid, Spain
Tarrés-Freixas, F:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
Campus Univ Autonoma Barcelona UAB, IRTA, Programa Sanitat Anim, Ctr Recerca Sanitat Anim CReSA, Bellaterra, Spain
Abancó, F:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
ISCIII, CIBERINFEC, Madrid, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
ISCIII, CIBERINFEC, Madrid, Spain
Germans Trias i Pujol Res Inst IGTP, Can Ruti Campus, Badalona, Spain
Pérez, M:
Campus Univ Autonoma Barcelona UAB, Unitat Mixta Invest IRTA UAB Sanitat Anim, Ctr Recerca Sanitat Anim CReSA, Bellaterra, Spain
Campus Univ Autonoma Barcelona UAB, IRTA, Programa Sanitat Anim, Ctr Recerca Sanitat Anim CReSA, Bellaterra, Spain
Vergara-Alert, J:
Campus Univ Autonoma Barcelona UAB, Unitat Mixta Invest IRTA UAB Sanitat Anim, Ctr Recerca Sanitat Anim CReSA, Bellaterra, Spain
Campus Univ Autonoma Barcelona UAB, IRTA, Programa Sanitat Anim, Ctr Recerca Sanitat Anim CReSA, Bellaterra, Spain
Segalés, J:
Campus Univ Autonoma Barcelona UAB, Unitat Mixta Invest IRTA UAB Sanitat Anim, Ctr Recerca Sanitat Anim CReSA, Bellaterra, Spain
Univ Autonoma Barcelona UAB, Dept Sanitat & Anat Anim, Fac Vet, Bellaterra, Spain
Carolis, C:
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain
Arranz, R:
Ctr Nacl Biotecnol CNB CSIC, Madrid, Spain
:
Hosp Germans Trias I Pujol, IrsiCaixa AIDS Res Inst, Campus Can Ruti, Badalona, Spain
ISCIII, CIBERINFEC, Madrid, Spain
Germans Trias i Pujol Res Inst IGTP, Can Ruti Campus, Badalona, Spain
Univ Vic, Cent Univ Catalonia UVic UCC, Fac Med, Infect Dis & Immun, Barcelona, Spain
Magri, G:
Hosp Mar Res Inst IMIM, Translat Clin Res Program, Barcelona, Spain
Univ Barcelona, Fac Med & Hlth Sci, Dept Biomed Sci, Immunol Unit, Barcelona, Spain
Green Published, gold
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