美国范德比尔特大学James E. Crowe等研究人员合作揭示乙型流感神经氨酸酶人类抗体的分离及气道界面保护机制。该项研究成果于2024年5月31日在线发表在《免疫》杂志上。

研究人员描述了从接种季节性疫苗的人体内分离出，识别乙型流感病毒（IBV）神经氨酸酶（NA）糖蛋白的人类单克隆抗体（mAb）。竞争结合实验表明，这些抗体能识别两个主要的抗原位点。其中一组包括mAb FluB-393，可广泛抑制IBV NA唾液酸酶活性，在体内起到预防保护作用，并与NA的侧角结合。

第二组包含一种活性位点mAb FluB-400，在体外原代人类呼吸道上皮细胞培养中可广泛抑制IBV NA 唾液酸酶活性和病毒复制，在体内全身或鼻内给药时可预防IBV。总之，这些研究结果通过展示两种保护人体免受IBV感染的mAb给药途径和确定潜在的IBV候选疗法，帮助人们从机制上理解了人体对IBV NA糖蛋白的免疫反应。

研究人员表示，IBV占流行性季节性人类流感病毒的很大一部分。

附：英文原文

Title: Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface

Author: Rachael M. Wolters, James A. Ferguson, Ivette A. Nuez, Elaine E. Chen, Ty Sornberger, Luke Myers, Svearike Oeverdieck, Sai Sundar Rajan Raghavan, Chandrahaas Kona, Laura S. Handal, Trevor E. Esilu, Edgar Davidson, Benjamin J. Doranz, Taylor B. Engdahl, Nurgun Kose, Lauren E. Williamson, C. Buddy Creech, Katherine N. Gibson-Corley, Andrew B. Ward, James E. Crowe

Issue&Volume: 2024-05-31

Abstract: Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonalhuman influenza viruses. Here, we describe the isolation of human monoclonal antibodies(mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individualfollowing seasonal vaccination. Competition-binding experiments suggested the antibodiesrecognized two major antigenic sites. One group, which included mAb FluB-393, broadlyinhibited IBV NA sialidase activity, protected prophylactically in vivo, and bound to the lateral corner of NA. The second group contained an active sitemAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replicationin vitro in primary human respiratory epithelial cell cultures and protected against IBV in vivo when administered systemically or intranasally. Overall, the findings described hereshape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV andthe identification of potential IBV therapeutic candidates.

DOI: 10.1016/j.immuni.2024.05.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00253-X