{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:19:34Z","timestamp":1790965174042,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Antibodies that mediate non-neutralizing functions play an important role in the immune response to Ebola virus (EBOV) and are thought to impact disease outcome. EBOV has also been associated with long term sequelae in survivors, however, the extent to which antibodies that mediate non-neutralizing functions are associated with the development of these sequelae is unknown. Here, the presence of antibodies mediating different effector functions and how they relate to long-term sequelae two years after the 2007 Bundibugyo Ebola virus (BDBV) outbreak was investigated. The majority of survivors demonstrated robust antibody effector functional activity and demonstrated persistent polyfunctional antibody profiles to the EBOV glycoprotein (GP) two years after infection. These functions were strongly associated with the levels of GP-specific IgG1. The odds of developing hearing loss, one of the more common sequelae to BDBV was reduced when antibodies mediating antibody dependent cellular phagocytosis (ADCP), antibody dependent complement deposition (ADCD), or activating NK cells (ADNKA) were observed. In addition, hearing loss was associated with increased levels of several pro-inflammatory cytokines and levels of these pro-inflammatory cytokines were associated with lower ADCP. These results are indicating that a skewed antibody profile and persistent inflammation may contribute to long term outcome in survivors of BDBV infection<\/jats:p>","DOI":"10.3389\/fimmu.2021.682120","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T07:47:44Z","timestamp":1621496864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Associations Between Antibody Fc-Mediated Effector Functions and Long-Term Sequelae in Ebola Virus Survivors"],"prefix":"10.3389","volume":"12","author":[{"given":"Dominic","family":"Paquin-Proulx","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn M.","family":"Gunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aljawharah","family":"Alrubayyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle V.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Creegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dohoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Kibuuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Millard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Wakabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh Anne","family":"Eller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson L.","family":"Michael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randal J.","family":"Schoepp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Hepburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa E.","family":"Hensley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merlin L.","family":"Robb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galit","family":"Alter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Eller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/v6103699","article-title":"A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response","volume":"6","author":"Roddy","year":"2014","journal-title":"Viruses"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0374","article-title":"Emerging Filoviral Disease in Uganda: Proposed Explanations and Research Directions","volume":"90","author":"Polonsky","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60667-8","article-title":"Ebola Haemorrhagic Fever","volume":"377","author":"Feldmann","year":"2011","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"102375","DOI":"10.1016\/j.jaut.2019.102375","article-title":"Ebola Virus Disease: An Emerging and Re-Emerging Viral Threat","volume":"106","author":"Rojas","year":"2020","journal-title":"J Autoimmun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3201\/eid1607.091525","article-title":"Ebola Hemorrhagic Fever Associated With Novel Virus Strain, Uganda, 2007-2008","volume":"16","author":"Wamala","year":"2010","journal-title":"Emerg Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e1000212","DOI":"10.1371\/journal.ppat.1000212","article-title":"Newly Discovered Ebola Virus Associated With Hemorrhagic Fever Outbreak in Uganda","volume":"4","author":"Towner","year":"2008","journal-title":"PloS Pathog"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70152-0","article-title":"Long-Term Sequelae After Ebola Virus Disease in Bundibugyo, Uganda: A Retrospective Cohort Study","volume":"15","author":"Clark","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1086\/514308","article-title":"Ebola Hemorrhagic Fever in Kikwit, Democratic Republic of the Congo: Clinical Observations in 103 Patients","author":"Bwaka","year":"1999","journal-title":"J Infect Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1086\/514318","article-title":"Clinical, Virologic, and Immunologic Follow-Up of Convalescent Ebola Hemorrhagic Fever Patients and Their Household Contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies a Kikwit","author":"Rowe","year":"1999","journal-title":"J Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz1062","article-title":"Long-Term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation","volume":"71","author":"Tozay","year":"2020","journal-title":"Clin Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa268","article-title":"Ebola-Specific CD8+ and CD4+ T-Cell Responses in Sierra Leonean Ebola Virus Survivors With or Without Post-Ebola Sequelae","volume":"222","author":"LaVergne","year":"2020","journal-title":"J Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3730","DOI":"10.1038\/s41467-020-17489-7","article-title":"Long-Lasting Severe Immune Dysfunction in Ebola Virus Disease Survivors","volume":"11","author":"Wiedemann","year":"2020","journal-title":"Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ijid.2018.06.022","article-title":"Ebola Vaccine Development: Systematic Review of Pre-Clinical and Clinical Studies, and Meta-Analysis of Determinants of Antibody Response Variability After Vaccination","volume":"74","author":"Gross","year":"2018","journal-title":"Int J Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nrmicro2129","article-title":"Correlates of Protective Immunity for Ebola Vaccines: Implications for Regulatory Approval by the Animal Rule","volume":"7","author":"Sullivan","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30165-8","article-title":"Determinants of Antibody Persistence Across Doses and Continents After Single-Dose rVSV-ZEBOV Vaccination for Ebola Virus Disease: An Observational Cohort Study","volume":"18","author":"Huttner","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix584","article-title":"Ebola Virus Neutralizing Antibodies Detectable in Survivors of Theyambuku, Zaire Outbreak 40 Years After Infection","volume":"217","author":"Rimoin","year":"2018","journal-title":"J Infect Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00107-16","article-title":"Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses","volume":"23","author":"Natesan","year":"2016","journal-title":"Clin Vaccine Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5224","article-title":"Protective Monotherapy Against Lethal Ebola Virus Infection by a Potently Neutralizing Antibody","volume":"351","author":"Corti","year":"2016","journal-title":"Science"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz364","article-title":"Survivors of Ebola Virus Disease Develop Polyfunctional Antibody Responses","volume":"221","author":"Gunn","year":"2020","journal-title":"J Infect Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy285","article-title":"Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in non-Human Primates","volume":"218","author":"Pascal","year":"2018","journal-title":"J Infect Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v10060286","article-title":"Post-Exposure Protection in Mice Against Sudan Virus by a Two Antibody Cocktail","volume":"10","author":"Froude","year":"2018","journal-title":"Viruses"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5788","article-title":"Isolation of Potent Neutralizing Antibodies From a Survivor of the 2014 Ebola Virus Outbreak","volume":"351","author":"Bornholdt","year":"2016","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy295","article-title":"Efficacy of Human Monoclonal Antibody Monotherapy Against Bundibugyo Virus Infection in Nonhuman Primates","volume":"218","author":"Gilchuk","year":"2018","journal-title":"J Infect Dis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"45552","DOI":"10.1038\/srep45552","article-title":"Antibody-Dependent-Cellular-Cytotoxicity-Inducing Antibodies Significantly Affect the Post-Exposure Treatment of Ebola Virus Infection","volume":"7","author":"Liu","year":"2017","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.chom.2018.07.009","article-title":"A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection Against Ebola Virus","volume":"24","author":"Gunn","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B26","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.cell.2018.07.033","article-title":"Systematic Analysis of Monoclonal Antibodies Against Ebola Virus GP Defines Features That Contribute to Protection","volume":"174","author":"Saphire","year":"2018","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.immuni.2021.03.009","article-title":"A Fc Engineering Approach to Define Functional Humoral Correlates of Immunity Against Ebola Virus","volume":"54","author":"Gunn","year":"2021","journal-title":"Immunity"},{"key":"B28","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jim.2019.05.006","article-title":"A Versatile High-Throughput Assay to Characterize Antibody-Mediated Neutrophil Phagocytosis","volume":"471","author":"Karsten","year":"2019","journal-title":"J Immunol Methods"},{"key":"B29","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.jim.2010.12.016","article-title":"A Robust, High-Throughput Assay to Determine the Phagocytic Activity of Clinical Antibody Samples","volume":"366","author":"Ackerman","year":"2011","journal-title":"J Immunol Methods"},{"key":"B30","doi-asserted-by":"publisher","first-page":"112630","DOI":"10.1016\/j.jim.2019.07.002","article-title":"A High-Throughput, Bead-Based, Antigen-Specific Assay to Assess the Ability of Antibodies to Induce Complement Activation","volume":"473","author":"Fischinger","year":"2019","journal-title":"J Immunol Methods"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2012.09.007","article-title":"High-Throughput, Multiplexed IgG Subclassing of Antigen-Specific Antibodies From Clinical Samples","volume":"386","author":"Brown","year":"2012","journal-title":"J Immunol Methods"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2742-5_11","article-title":"Multiplexed Microsphere Suspension Array-Based Immunoassays","volume":"1318","author":"Lin","year":"2015","journal-title":"Methods Mol Biol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0007654","DOI":"10.1371\/journal.pntd.0007654","article-title":"Serological Analysis of Ebola Virus Survivors and Close Contacts in Sierra Leone: A Cross-Sectional Study","volume":"13","author":"Halfmann","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30736-2","article-title":"Longitudinal Antibody and T Cell Responses in Ebola Virus Disease Survivors and Contacts: An Observational Cohort Study","volume":"21","author":"Thom","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix619","article-title":"Serologic Evidence of Ebolavirus Infection in a Population With No History of Outbreaks in the Democratic Republic of the Congo","volume":"217","author":"Mulangu","year":"2018","journal-title":"J Infect Dis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy251","article-title":"Suspected Exposure to Filoviruses Among People Contacting Wildlife in Southwestern Uganda","volume":"218","author":"Smiley Evans","year":"2018","journal-title":"J Infect Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e9126","DOI":"10.1371\/journal.pone.0009126","article-title":"High Prevalence of Both Humoral and Cellular Immunity to Zaire Ebolavirus Among Rural Populations in Gabon","volume":"5","author":"Becquart","year":"2010","journal-title":"PloS One"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nm1511","article-title":"Microbial Translocation is a Cause of Systemic Immune Activation in Chronic HIV Infection","volume":"12","author":"Brenchley","year":"2006","journal-title":"Nat Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1502619112","article-title":"Human Ebola Virus Infection Results in Substantial Immune Activation","volume":"112","author":"McElroy","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03146-y","article-title":"Ebola Virus Antibody Decay-Stimulation in a High Proportion of Survivors","volume":"590","author":"Adaken","year":"2021","journal-title":"Nature"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01292-y","article-title":"Attributes and Predictors of Long COVID","volume":"27","author":"Sudre","year":"2021","journal-title":"Nat Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01283-z","article-title":"Post-Acute COVID-19 Syndrome","volume":"27","author":"Nalbandian","year":"2021","journal-title":"Nat Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"jrm00063","DOI":"10.2340\/16501977-2694","article-title":"Long-Term Clinical Outcomes in Survivors of Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome Coronavirus Outbreaks After Hospitalisation or ICU Admission: A Systematic Review and Meta-Analysis","volume":"52","author":"Ahmed","year":"2020","journal-title":"J Rehabil Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.190162","article-title":"Chronic Joint Pain 3 Years After Chikungunya Virus Infection Largely Characterized by Relapsing-remitting Symptoms","volume":"47","author":"Tritsch","year":"2020","journal-title":"J Rheumatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.682120\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T07:47:46Z","timestamp":1621496866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.682120\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,20]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2021.682120"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.682120","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,20]]},"article-number":"682120"}}