Feldman Jared, Ramos Ana Sofia Ferreira, Vu Mya, Maurer Daniel P, Rosado Victoria C, Lingwood Daniel, Bajic Goran, Schmidt Aaron G
Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Sci Immunol. 2025 Jan 24;10(103):eado9572. doi: 10.1126/sciimmunol.ado9572.
Understanding the naïve B cell repertoire and its specificity for potential zoonotic threats, such as the highly pathogenic avian influenza (HPAI) H5Nx viruses, may allow prediction of infection- or vaccine-specific responses. However, this naïve repertoire and the possibility to respond to emerging, prepandemic viruses are largely undetermined. Here, we profiled naïve B cell reactivity against a prototypical HPAI H5 hemagglutinin (HA), the major target of antibody responses. We found that the frequency of H5-specific human naïve B cells targeting the HA "head" domain was increased relative to cross-reactive B cells to a circulating seasonal H1N1 strain. We classified the isolated monoclonal antibodies (mAbs) by the HA epitopes engaged and found that selected mAbs neutralized H5N1 at germline. We determined a cryo-electron microscopic structure of one mAb in complex with H5 HA to define its epitope. Our study defines the naïve human B cell repertoire recognizing a potentially zoonotic HPAI.
了解初始B细胞库及其对潜在人畜共患病威胁（如高致病性禽流感（HPAI）H5Nx病毒）的特异性，可能有助于预测感染或疫苗特异性反应。然而，这种初始库以及对新出现的大流行前病毒作出反应的可能性在很大程度上尚未确定。在这里，我们分析了初始B细胞对典型HPAI H5血凝素（HA）（抗体反应的主要靶点）的反应性。我们发现，与针对循环季节性H1N1毒株的交叉反应性B细胞相比，靶向HA“头部”结构域的H5特异性人类初始B细胞频率有所增加。我们根据所涉及的HA表位对分离出的单克隆抗体（mAb）进行分类，发现所选mAb在胚系状态下可中和H5N1。我们确定了一种mAb与H5 HA复合物的冷冻电子显微镜结构，以确定其表位。我们的研究定义了识别潜在人畜共患病HPAI的人类初始B细胞库。
