Conserved sites on the influenza H1 and H3 hemagglutinin recognized by human antibodies

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-04-23 DOI:10.1126/sciadv.adu9140

Daniel P. Maurer, Mya Vu, Ana Sofia Ferreira Ramos, Haley L. Dugan, Paul Khalife, James C. Geoghegan, Laura M. Walker, Goran Bajic, Aaron G. Schmidt

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Abstract

Monoclonal antibodies (mAbs) targeting the influenza hemagglutinin (HA) can be used as prophylactics or templates for next-generation vaccines. Here, we isolated broad, subtype-neutralizing mAbs from human B cells recognizing the H1 or H3 HA “head” and a mAb engaging the conserved stem. The H1 mAbs bind the lateral patch epitope on HAs from 1933 to 2021 and a prepandemic swine H1N1 virus. We improved neutralization potency using directed evolution toward a contemporary H1 HA. Deep mutational scanning of four antigenically distinct H1N1 viruses identified potential viral escape pathways. For the H3 mAbs, we used cryo–electron microscopy to define their epitopes: One mAb binds the side of the HA head, accommodating the N133 glycan and a pocket underneath the receptor binding site; the other mAb recognizes an HA stem epitope that partially overlaps with previously characterized mAbs but with distinct antibody variable genes. Collectively, these mAbs identify conserved sites recognized by broadly-reactive mAbs that may be elicited by next-generation vaccines.

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人类抗体识别的流感 H1 和 H3 血凝素上的保守位点

针对流感血凝素（HA）的单克隆抗体（mab）可作为下一代疫苗的预防或模板。在这里，我们从人B细胞中分离出广泛的、亚型中和的单克隆抗体，识别H1或H3 HA“头”和一个与保守的干细胞结合的单克隆抗体。H1单克隆抗体结合1933年至2021年的ha和大流行前的猪H1N1病毒的外侧斑块表位。我们利用现代H1 HA的定向进化提高了中和效力。对四种抗原性不同的H1N1病毒进行深度突变扫描，确定了潜在的病毒逃逸途径。对于H3单抗，我们使用低温电子显微镜来确定它们的表位：一个单抗结合HA头部的一侧，容纳N133聚糖和受体结合位点下方的口袋；另一种单克隆抗体识别HA干表位，该表位与先前鉴定的单克隆抗体部分重叠，但具有不同的抗体可变基因。总的来说，这些单克隆抗体鉴定出被广泛反应性单克隆抗体识别的保守位点，这些位点可能被下一代疫苗激发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.