Vaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem–specific human B cells

IF 15.8 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-01-01 DOI:10.1126/scitranslmed.adr8373

Grace E. Mantus, Ankita J. Chopde, Jason Gorman, Lauren Y. Cominsky, Amine Ourahmane, Adrian Creanga, Geoffrey D. Shimberg, Rebecca A. Gillespie, David J. Van Wazer, Tongqing Zhou, Suprabhath R. Gajjala, Connor Williams, Emma Maestle, Douglas S. Reed, Leonid Serebryannyy, Pamela Costner, Lasonji Holman, Joseph P. Casazza, Richard A. Koup, Lesia K. Dropulic, Peter D. Kwong, Adrian B. McDermott, Masaru Kanekiyo, Sarah F. Andrews

{"title":"Vaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem–specific human B cells","authors":"Grace E. Mantus, Ankita J. Chopde, Jason Gorman, Lauren Y. Cominsky, Amine Ourahmane, Adrian Creanga, Geoffrey D. Shimberg, Rebecca A. Gillespie, David J. Van Wazer, Tongqing Zhou, Suprabhath R. Gajjala, Connor Williams, Emma Maestle, Douglas S. Reed, Leonid Serebryannyy, Pamela Costner, Lasonji Holman, Joseph P. Casazza, Richard A. Koup, Lesia K. Dropulic, Peter D. Kwong, Adrian B. McDermott, Masaru Kanekiyo, Sarah F. Andrews","doi":"10.1126/scitranslmed.adr8373","DOIUrl":null,"url":null,"abstract":"The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10). Epitope mapping revealed two epitope supersites on the group 2 stem. Antibodies targeting the central epitope were broadly cross-reactive, whereas antibodies targeting the lower epitope had narrower breadth but higher potency against H3 subtypes. The ratio of B cells targeting each of the supersites varied with the vaccine subtype, leading to differences in the cross-reactivity of the B cell response. Our findings suggest that vaccine strategies targeting both group 2 stem epitopes would be complementary, eliciting broader and more potent protection against both seasonal and pandemic influenza strains.","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"114 1","pages":""},"PeriodicalIF":15.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1126/scitranslmed.adr8373","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10). Epitope mapping revealed two epitope supersites on the group 2 stem. Antibodies targeting the central epitope were broadly cross-reactive, whereas antibodies targeting the lower epitope had narrower breadth but higher potency against H3 subtypes. The ratio of B cells targeting each of the supersites varied with the vaccine subtype, leading to differences in the cross-reactivity of the B cell response. Our findings suggest that vaccine strategies targeting both group 2 stem epitopes would be complementary, eliciting broader and more potent protection against both seasonal and pandemic influenza strains.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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.