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, Tarrés-Freixas Ferran, Abancó Ferran, Urrea Victor, Izquierdo-Useros Nuria, Riveira-Muñoz Eva, Ballana Ester, Pérez Mónica, Vergara-Alert Júlia, Segalés Joaquim, Carolis Carlo, Arranz Rocío, Blanco Julià, Magri Giuliana
Translational Clinical Research Program, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Nat Commun. 2024 Feb 5;15(1):1051. doi: 10.1038/s41467-024-45171-9.
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.
在此，我们报告了17T2的特性，这是一种从在第一波疫情大流行期间感染的新冠康复者体内分离出的可中和新冠病毒（SARS-CoV-2）的人源单克隆抗体。17T2是一种1类VH1-58/κ3-20抗体，源自受体结合域（RBD）特异性IgA记忆B细胞，对包括XBB.1.16和BA.2.86奥密克戎亚变体在内的既往和新型SARS-CoV-2变体具有广泛的中和活性。同样，17T2在K18-hACE2小鼠中对奥密克戎BA.1.1感染表现出体内预防和治疗活性。冷冻电子显微镜重建显示，与其他结构相似的抗体（包括S2E12）一样，17T2以“向上”位置的RBD结合BA.1刺突蛋白，并阻断受体结合基序。然而，与S2E12不同的是，17T2对所有测试变体均保留其中和活性，这可能是由于其与RBD的接触面积更大。这些结果突出了抗体结构微小变化对中和性能的影响，并确定17T2为未来临床干预的潜在候选物。
