{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:00:44Z","timestamp":1787238044917,"version":"build-2736575974"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["HHSN272201400024C"],"award-info":[{"award-number":["HHSN272201400024C"]}]},{"name":"NIH\/NIAID","award":["U01 AI150739"],"award-info":[{"award-number":["U01 AI150739"]}]},{"name":"NIH\/NCATS","award":["UL1 TR002243"],"award-info":[{"award-number":["UL1 TR002243"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,8]]},"abstract":"<jats:p>Avian H7N9 influenza viruses cause sporadic outbreaks of human infections and threaten to cause a major pandemic. The breadth of B cell responses to natural infection and the dominant antigenic sites recognized during first exposure to H7 HA following infection are incompletely understood. Here, we studied the B cell response to H7 HA of 2 individuals who had recovered from natural H7N9 virus infection. We used competition binding, hydrogen-deuterium mass spectrometry, and single-particle negative stain electron microscopy to identify the patterns of molecular recognition of the antibody responses to H7 HA. We found that circulating H7-reactive B cells recognized a diverse antigenic landscape on the HA molecule, including HA head domain epitopes in antigenic sites A and B and in the trimer interface-II region and epitopes in the stem region. Most H7 antibodies exhibited little heterosubtypic breadth, but many recognized a wide diversity of unrelated H7 strains. We tested the antibodies for functional activity and identified clones with diverse patterns of inhibition, including neutralizing, hemagglutination- or egress-inhibiting, or HA trimer\u2013disrupting activities. Thus, the human B cell response to primary H7 natural infection is diverse, highly functional, and broad for recognition of diverse H7 strains.<\/jats:p>","DOI":"10.1172\/jci.insight.152403","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T12:00:39Z","timestamp":1629979239000},"source":"Crossref","is-referenced-by-count":11,"title":["Human antibody recognition of H7N9 influenza virus HA following natural infection"],"prefix":"10.1172","volume":"6","author":[{"given":"Iuliia M.","family":"Gilchuk","sequence":"first","affiliation":[{"name":"Vanderbilt Vaccine Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7994-4693","authenticated-orcid":true,"given":"Sandhya","family":"Bangaru","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurgun","family":"Kose","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin G.","family":"Bombardi","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Trivette","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-6809","authenticated-orcid":true,"given":"Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4745-8057","authenticated-orcid":true,"given":"Hannah L.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5230-1532","authenticated-orcid":true,"given":"Robert H.","family":"Carnahan","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center and"},{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-3769","authenticated-orcid":true,"given":"Andrew B.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"James E.","family":"Crowe","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Center and"},{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA."},{"name":"Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"issue":"5","key":"B1","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1128\/JVI.79.5.2814-2822.2005","article-title":"Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls","volume":"79","author":"Fouchier","year":"2005","journal-title":"J Virol"},{"issue":"3","key":"B2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0090826","article-title":"Sampling strategies and biodiversity of influenza A subtypes in wild birds","volume":"9","author":"Olson","year":"2014","journal-title":"PLoS One"},{"issue":"3\u20134","key":"B3","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.vetmic.2011.06.011","article-title":"Genetic characterization of H7N2 influenza virus isolated from pigs","volume":"153","author":"Kwon","year":"2011","journal-title":"Vet Microbiol"},{"issue":"9","key":"B4","doi-asserted-by":"crossref","DOI":"10.3390\/v10090497","article-title":"Zoonotic potential of influenza A viruses: a comprehensive overview","volume":"10","author":"Mostafa","year":"2018","journal-title":"Viruses"},{"issue":"12","key":"B5","first-page":"142","article-title":"Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness","volume":"93","author":"[No authors listed]","year":"2018","journal-title":"Wkly Epidemiol Rec"},{"issue":"12","key":"B6","first-page":"109","article-title":"Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness","volume":"90","author":"[No authors listed]","year":"2019","journal-title":"Wkly Epidemiol Rec"},{"issue":"21","key":"B7","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2019.24.21.1900273","article-title":"The re-emergence of highly pathogenic avian influenza H7N9 viruses in humans in mainland China, 2019","volume":"24","author":"Yu","year":"2019","journal-title":"Euro Surveill"},{"key":"B8","unstructured":"WHO. Human infection with avian influenza A(H7N9) virus \u2014 China: Update. https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/05-september-2018-ah7n9-china-en Updated September 5, 2018. Accessed September 3, 2021"},{"issue":"4","key":"B9","doi-asserted-by":"crossref","first-page":"663","DOI":"10.3201\/eid2404.171995","article-title":"Influenza A(H7N9) virus antibody responses in survivors 1 year after infection, China, 2017","volume":"24","author":"Ma","year":"2018","journal-title":"Emerg Infect Dis"},{"issue":"2","key":"B10","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/irv.12702","article-title":"Persistence of H7N9 virus antibody response 2 years after infection","volume":"14","author":"Yao","year":"2020","journal-title":"Influenza Other Respir Viruses"},{"issue":"3","key":"B11","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jinf.2019.11.024","article-title":"Specificity, kinetics and longevity of antibody responses to avian influenza A(H7N9) virus infection in humans","volume":"80","author":"Chen","year":"2020","journal-title":"J Infect"},{"issue":"2","key":"B12","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3201\/eid2002.131094","article-title":"Human antibody responses to avian influenza A(H7N9) virus, 2013","volume":"20","author":"Guo","year":"2014","journal-title":"Emerg Infect Dis"},{"issue":"6","key":"B13","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/femsre\/fuz019","article-title":"Global patterns of avian influenza A (H7): virus evolution and zoonotic threats","volume":"43","author":"Naguib","year":"2019","journal-title":"FEMS Microbiol Rev"},{"key":"B14","article-title":"Limited antigenic diversity in contemporary H7 avian-origin influenza A viruses from North America","volume":"6","author":"Xu","year":"2016","journal-title":"Sci Rep"},{"issue":"42","key":"B15","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1016\/j.vaccine.2013.08.040","article-title":"H7N3 live attenuated influenza vaccine has a potential to protect against new H7N9 avian influenza virus","volume":"31","author":"Rudenko","year":"2013","journal-title":"Vaccine"},{"issue":"8","key":"B16","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1128\/CVI.00272-14","article-title":"An H7N1 influenza virus vaccine induces broadly reactive antibody responses against H7N9 in humans","volume":"21","author":"Krammer","year":"2014","journal-title":"Clin Vaccine Immunol"},{"issue":"3","key":"B17","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0246613","article-title":"Hemagglutination inhibition (HAI) antibody landscapes after vaccination with H7Nx virus like particles","volume":"16","author":"Jang","year":"2021","journal-title":"PLoS One"},{"issue":"1","key":"B18","doi-asserted-by":"crossref","DOI":"10.1038\/s41426-018-0115-0","article-title":"Cross-reactive mouse monoclonal antibodies raised against the hemagglutinin of A\/Shanghai\/1\/2013 (H7N9) protect against novel H7 virus isolates in the mouse model","volume":"7","author":"Stadlbauer","year":"2018","journal-title":"Emerg Microbes Infect"},{"issue":"4","key":"B19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005578","article-title":"Broadly-reactive neutralizing and non-neutralizing antibodies directed against the H7 influenza virus hemagglutinin reveal divergent mechanisms of protection","volume":"12","author":"Tan","year":"2016","journal-title":"PLoS Pathog"},{"issue":"5","key":"B20","doi-asserted-by":"crossref","first-page":"e01850","DOI":"10.1128\/JVI.01850-17","article-title":"Structural insight into a human neutralizing antibody against influenza virus H7N9","volume":"92","author":"Chen","year":"2018","journal-title":"J Virol"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2019.104556","article-title":"A cross-reactive human monoclonal antibody targets the conserved H7 antigenic site A from fifth wave H7N9-infected humans","volume":"170","author":"Li","year":"2019","journal-title":"Antivir Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136032"},{"issue":"2","key":"B23","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/s41564-018-0303-7","article-title":"Structure-function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans","volume":"4","author":"Huang","year":"2019","journal-title":"Nat Microbiol"},{"issue":"4","key":"B24","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/infdis\/jiw608","article-title":"Induction of broadly cross-reactive stalk-specific antibody responses to influenza group 1 and group 2 hemagglutinins by natural H7N9 virus infection in humans","volume":"215","author":"Liu","year":"2017","journal-title":"J Infect Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74374"},{"issue":"6313","key":"B26","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1126\/science.aag1322","article-title":"Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting","volume":"354","author":"Gostic","year":"2016","journal-title":"Science"},{"issue":"1","key":"B27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3201\/eid2201.151330","article-title":"Avian influenza A(H7N9) virus infection in 2 travelers returning from China to Canada, January 2015","volume":"22","author":"Skowronski","year":"2016","journal-title":"Emerg Infect Dis"},{"issue":"suppl 6","key":"B28","doi-asserted-by":"crossref","first-page":"G47","DOI":"10.1016\/j.vaccine.2009.10.124","article-title":"Recent advances in the study of human antibody responses to influenza virus using optimized human hybridoma approaches","volume":"27","author":"Crowe","year":"2009","journal-title":"Vaccine"},{"issue":"1","key":"B29","doi-asserted-by":"crossref","first-page":"AID","DOI":"10.1128\/microbiolspec.AID-0027-2014","article-title":"Use of human hybridoma technology to isolate human monoclonal antibodies","volume":"3","author":"Smith","year":"2015","journal-title":"Microbiol Spectr"},{"issue":"12","key":"B30","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.3201\/eid1012.040961","article-title":"Human illness from avian influenza H7N3, British Columbia","volume":"10","author":"Tweed","year":"2004","journal-title":"Emerg Infect Dis"},{"issue":"12","key":"B31","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.3201\/eid2312.170798","article-title":"Avian influenza A(H7N2) virus in human exposed to sick cats, New York, USA, 2016","volume":"23","author":"Marinova-Petkova","year":"2017","journal-title":"Emerg Infect Dis"},{"issue":"15","key":"B32","doi-asserted-by":"crossref","first-page":"e00672","DOI":"10.1128\/JVI.00672-17","article-title":"A novel A(H7N2) influenza virus isolated from a veterinarian caring for cats in a New York City animal shelter causes mild disease and transmits poorly in the ferret model","volume":"91","author":"Belser","year":"2017","journal-title":"J Virol"},{"issue":"12","key":"B33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0080034","article-title":"Mechanisms of hemagglutinin targeted influenza virus neutralization","volume":"8","author":"Brandenburg","year":"2013","journal-title":"PLoS One"},{"issue":"5","key":"B34","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.cell.2019.04.011","article-title":"A site of vulnerability on the influenza virus hemagglutinin head domain trimer interface","volume":"177","author":"Bangaru","year":"2019","journal-title":"Cell"},{"issue":"1","key":"B35","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-04704-9","article-title":"A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA","volume":"9","author":"Bangaru","year":"2018","journal-title":"Nat Commun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85317"},{"issue":"3","key":"B37","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.cell.2016.05.073","article-title":"Structure and function analysis of an antibody recognizing all influenza A subtypes","volume":"166","author":"Kallewaard","year":"2016","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.06.013"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.05.014"},{"issue":"4","key":"B40","doi-asserted-by":"crossref","first-page":"e01526","DOI":"10.1128\/JVI.01526-18","article-title":"Hemagglutinin stalk-reactive antibodies interfere with influenza virus neuraminidase activity by steric hindrance","volume":"93","author":"Chen","year":"2019","journal-title":"J Virol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.10.003"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01085-13"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2009.01.002"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2009.01.004"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2003.08.005"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1021\/bi9008853"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.224535"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560020404"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.5501\/wjv.v5.i2.85"},{"key":"B50","unstructured":"McKinney W. Data Structures for Statistical Computing in Python. Paper presented at: Proceedings of the 9th Python in Science Conference (SciPy 2010); June 28\u2013July 3, 2010; Austin, Texas, USA. https:\/\/conference.scipy.org\/proceedings\/scipy2010\/mckinney.html Accessed September 3, 2021"},{"issue":"W 1","key":"B51","doi-asserted-by":"crossref","first-page":"W256","DOI":"10.1093\/nar\/gkz239","article-title":"Interactive tree of life (iTOL) v4: recent updates and new developments","volume":"47","author":"Letunic","year":"2019","journal-title":"Nucleic Acids Res"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/152403\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:43:28Z","timestamp":1779147808000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/152403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":51,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10,8]]},"published-print":{"date-parts":[[2021,10,8]]}},"alternative-id":["10.1172\/jci.insight.152403"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.152403","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]},"article-number":"e152403"}}