美国伊利诺伊大学香槟分校 生物化学系Nicholas C. Wu团队探明，利用疫苗诱导的保护性抗体确定流感N2神经氨酸酶(NA)的保守表位。2023年11月14日出版的《免疫》杂志发表了这项成果。

他们从单个疫苗接种者的质母细胞中分离出三种广泛反应的N2抗体，包括一种与来自50年季节性H3N2株的NAs交叉反应的抗体。尽管这三种抗体具有不同的种系用途，但它们识别的相似表位不是靠近NA活性位点，而是涉及NA头部结构域高度保守的下侧。他们还发现，由于Fc效应和通过位阻抑制NA，这三种抗体在体内都具有预防和治疗保护作用。此外，Fc效应物在体内的保护作用与体外的病毒生长抑制活性呈负相关。

总的来说，他们的研究结果促进了对NA抗体反应的理解，并为开发广泛保护性流感疫苗提供了重要见解。

研究人员表示，NA作为流感疫苗靶点的价值越来越高;然而，其抗原性仍不清楚。

附：英文原文

Title: Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase

Author: Ruipeng Lei, Wooseob Kim, Huibin Lv, Zongjun Mou, Michael J. Scherm, Aaron J. Schmitz, Jackson S. Turner, Timothy J.C. Tan, Yiquan Wang, Wenhao O. Ouyang, Weiwen Liang, Joel Rivera-Cardona, Chuyun Teo, Claire S. Graham, Christopher B. Brooke, Rachel M. Presti, Chris K.P. Mok, Florian Krammer, Xinghong Dai, Ali H. Ellebedy, Nicholas C. Wu

Issue&Volume: 2023/11/14

Abstract: There is growing appreciation for neuraminidase (NA) as an influenza vaccine target;however, its antigenicity remains poorly characterized. In this study, we isolatedthree broadly reactive N2 antibodies from the plasmablasts of a single vaccinee, includingone that cross-reacts with NAs from seasonal H3N2 strains spanning five decades. Althoughthese three antibodies have diverse germline usages, they recognize similar epitopesthat are distant from the NA active site and instead involve the highly conservedunderside of NA head domain. We also showed that all three antibodies confer prophylacticand therapeutic protection in vivo, due to both Fc effector functions and NA inhibition through steric hindrance. Additionally,the contribution of Fc effector functions to protection in vivo inversely correlates with viral growth inhibition activity in vitro. Overall, our findings advance the understanding of NA antibody response and provideimportant insights into the development of a broadly protective influenza vaccine.

DOI: 10.1016/j.immuni.2023.10.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00445-4