Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques

IF 14.6 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-09-10 DOI:10.1126/scitranslmed.ady3570

Maya Sangesland, Ning Li, Yaroslav Tsybovsky, Megan D. Rodgers, Julianna Han, Alesandra J. Rodriguez, James A. Ferguson, Amy R. Henry, Sarah C. Smith, Jesmine Roberts-Torres, Rebecca A. Gillespie, Cuiping Liu, Jonah S. Merriam, Tyler Stephens, Connor Williams, Emma Walker, Martin Corcoran, Michelle Ravichandran, Adrian Creanga, Sarah F. Andrews, Theodore C. Pierson, Gunilla B. Karlsson Hedestam, Chaim A. Schramm, Douglas S. Reed, Daniel C. Douek, Tongqing Zhou, Andrew B. Ward, Masaru Kanekiyo

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引用次数: 0

Abstract

Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V_H1-138, the macaque homolog of human V_H1-69, a V_H gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs containing the canonical NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded structural motifs. These findings indicate that the macaque immunoglobulin repertoire can support humanlike public bnAb responses to influenza HA, highlighting the value of the macaque model for translational vaccinology. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans have been similarly shaped during evolution.

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人类和猕猴之间流感免疫的功能、免疫遗传学和结构趋同

人类B细胞对流感血凝素（HA）干细胞（一种通用的疫苗靶点）的免疫往往是刻板的，免疫遗传学上受到限制，这给人类以外的研究带来了障碍。在这里，我们展示了接种了HA干细胞免疫原的食蟹猕猴，引发了类似人类的公共B细胞谱系，靶向两个主要的保守易感位点，中央干细胞和锚定表位。中心干抗体主要来源于VH1-138，这是人类VH1-69的猕猴同源物，VH基因优先用于人类中心干广泛中和抗体（bnAbs）。同样，猕猴也产生了包含典型NWP基序的锚定bnab。这两种bnAb谱系在功能和结构上都与人类相似，识别主要由种系编码的结构基序介导。这些发现表明，猕猴免疫球蛋白库可以支持对流感HA的类似人的公共bnAb反应，突出了猕猴模型在转化疫苗学中的价值。此外，这强调了同源种系编码免疫的效用，表明猕猴和人类的免疫库在进化过程中具有相似的形状。

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 Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.