小柯机器人

瑞士Vir生物技术公司Matteo Samuele Pizzuto等研究人员合作开发出一种通过受体模拟抑制神经氨酸酶的泛流感抗体。2023年5月31日，《自然》杂志在线发表了这项成果。

研究人员描述了一种神经氨酸酶靶向单克隆抗体FNI9，它能有效地抑制所有第1组和第2组甲型流感病毒（IAV）以及Victoria/2/87-样、Yamagata/16/88-样和原始乙型流感病毒（IBV）的酶活性。FNI9能广泛地中和季节性IAV和IBV，包括在245位上带有N-聚糖的免疫性H3N2毒株，当与抗血凝素干的抗体结合时，显示出协同活性。结构分析显示，FNI9重链互补性决定区3中的D107模拟了唾液酸羧基与神经氨酸酶催化部位的三个高度保守精氨酸残基（R118、R292和R371）的相互作用。FNI9对小鼠中致命的IAV和IBV感染显示出有效的预防活性。FNI9单克隆抗体前所未有的广泛性和有效性支持其开发用于预防季节性和大流行性病毒的流感疾病。

据悉，快速演变的IAV和IBV是下呼吸道感染复发的主要原因。目前的流感疫苗主要是针对血凝素的高度可变头部区域产生抗体，其有效性受到病毒漂移和不理想免疫反应的限制。

附：英文原文

Title: A pan-influenza antibody inhibiting neuraminidase via receptor mimicry

Author: Momont, Corey, Dang, Ha V., Zatta, Fabrizia, Hauser, Kevin, Wang, Caihong, di Iulio, Julia, Minola, Andrea, Czudnochowski, Nadine, De Marco, Anna, Branch, Kaitlin, Donermeyer, David, Vyas, Siddhant, Chen, Alex, Ferri, Elena, Guarino, Barbara, Powell, Abigail E., Spreafico, Roberto, Yim, Samantha S., Balce, Dale R., Bartha, Istvan, Meury, Marcel, Croll, Tristan I., Belnap, David M., Schmid, Michael A., Schaiff, William Timothy, Miller, Jessica L., Cameroni, Elisabetta, Telenti, Amalio, Virgin, Herbert W., Rosen, Laura E., Purcell, Lisa A., Lanzavecchia, Antonio, Snell, Gyorgy, Corti, Davide, Pizzuto, Matteo Samuele

Issue&Volume: 2023-05-31

Abstract: Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift1 and suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses.

DOI: 10.1038/s41586-023-06136-y

Source: https://www.nature.com/articles/s41586-023-06136-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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