保护性人源单克隆抗体靶向流感病毒神经氨酸酶底部的易受攻击的保守位点，这一成果由美国国立卫生研究院Masaru Kanekiyo小组经过不懈努力而取得。相关论文发表在2024年3月1日出版的国际学术期刊《免疫》上。

研究组描述了神经氨酸酶特异性的人源抗体，其靶向神经氨酸酶头部区域的底部，抑制多种人类H3N2、猪源变异H3N2和H2N2病毒的传播，在小鼠身上，既在暴露前又在暴露后提供对致命H3N2感染的保护。这两种抗体与神经氨酸酶复合物的冷冻电镜结构显示，其覆盖神经氨酸酶头部下侧的非重叠表位。

这些位点在N2神经氨酸酶中是高度保守的，除非神经氨酸酶头倾斜或解离，否则无法进入。他们发现通过识别神经氨酸酶底部隐藏的保守易受攻击位点，有助于指导针对不断变化流感病毒的有效对策的发展。

据悉，不断进化的流感病毒引发季节性流行病，并构成全球大流行的威胁。虽然病毒神经氨酸酶是一种有效的药物和疫苗靶点，但对神经氨酸酶抗原图谱的了解仍然不完整。

附：英文原文

Title: Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase

Author: Julia Lederhofer, Yaroslav Tsybovsky, Lam Nguyen, Julie E. Raab, Adrian Creanga, Tyler Stephens, Rebecca A. Gillespie, Hubza Z. Syeda, Brian E. Fisher, Michelle Skertic, Christina Yap, Andrew J. Schaub, Reda Rawi, Peter D. Kwong, Barney S. Graham, Adrian B. McDermott, Sarah F. Andrews, Neil P. King, Masaru Kanekiyo

Issue&Volume: 2024-03-01

Abstract: Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the NA antigenic landscape still remains incomplete. Here, we describe NA-specific human antibodies that target the underside of the NA globular head domain, inhibit viral propagation of a wide range of human H3N2, swine-origin variant H3N2, and H2N2 viruses, and confer both pre- and post-exposure protection against lethal H3N2 infection in mice. Cryo-EM structures of two such antibodies in complex with NA reveal non-overlapping epitopes covering the underside of the NA head. These sites are highly conserved among N2 NAs yet inaccessible unless the NA head tilts or dissociates. Our findings help guide the development of effective countermeasures against ever-changing influenza viruses by identifying hidden conserved sites of vulnerability on the NA underside.

DOI: 10.1016/j.immuni.2024.02.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00079-7