{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:45:52Z","timestamp":1780098352699,"version":"3.54.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The re-emergence of Zika virus (ZIKV) caused widespread infections that were linked to Guillain-Barr\u00e9 syndrome in adults and congenital malformation in fetuses, and epidemiological data suggest that ZIKV infection can induce protective antibody responses. A more detailed understanding of anti-ZIKV antibody responses may lead to enhanced antibody discovery and improved vaccine designs against ZIKV and related flaviviruses. Here, we applied recently-invented library-scale antibody screening technologies to determine comprehensive functional molecular and genetic profiles of naturally elicited human anti-ZIKV antibodies in three convalescent individuals. We leveraged natively paired antibody yeast display and NGS to predict antibody cross-reactivities and coarse-grain antibody affinities, to perform in-depth immune profiling of IgM, IgG, and IgA antibody repertoires in peripheral blood, and to reveal virus maturation state-dependent antibody interactions. Repertoire-scale comparison of ZIKV VLP-specific and non-specific antibodies in the same individuals also showed that mean antibody somatic hypermutation levels were substantially influenced by donor-intrinsic characteristics. These data provide insights into antiviral antibody responses to ZIKV disease and outline systems-level strategies to track human antibody immune responses to emergent viral infections.<\/jats:p>","DOI":"10.3389\/fimmu.2021.615102","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T04:55:27Z","timestamp":1614142527000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Ahmed S.","family":"Fahad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan R.","family":"Timm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Madan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E.","family":"Burgomaster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Dowd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Normandin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas F.","family":"Guti\u00e9rrez-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Pennington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Oliveira","family":"De Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Laboune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingshu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Ambrozak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingelise J.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Douek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Ledgerwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barney S.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda R.","family":"Castilho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore C.","family":"Pierson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mascola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon J.","family":"DeKosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix383","article-title":"Pandemic Zika: A Formidable Challenge to Medicine and Public Health","volume":"216","author":"Morens","year":"2017","journal-title":"J Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0446-y","article-title":"The emergence of Zika virus and its new clinical syndromes","volume":"560","author":"Pierson","year":"2018","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa1602412","article-title":"Zika Virus Infection in Pregnant Women in Rio de Janeiro","volume":"375","author":"Brasil","year":"2016","journal-title":"New Engl J Med"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMsr1604338","article-title":"Zika Virus and Birth Defects \u2014 Reviewing the Evidence for Causality","volume":"374","author":"Rasmussen","year":"2016","journal-title":"New Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00562-6","article-title":"Guillain-Barr\u00e9 Syndrome outbreak associated with Zika virus infection inFrench Polynesia: a case-control study","volume":"387","author":"Cao-Lormeau","year":"2016","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.coviro.2012.12.001","article-title":"Flaviviruses: braking the entering","volume":"3","author":"Pierson","year":"2013","journal-title":"Curr Opin Virol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.11.5480-5491.2002","article-title":"Folding and Dimerization of Tick-Borne Encephalitis Virus Envelope Proteins prM and Ein the Endoplasmic Reticulum","volume":"76","author":"Lorenz","year":"2002","journal-title":"J Virol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.chom.2016.04.013","article-title":"Structures of the Zika Virus Envelope Protein and Its Complex with a FlavivirusBroadly Protective Antibody","volume":"19","author":"Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature20564","article-title":"Neutralizing human antibodies prevent Zika virus replication and fetal disease inmice","volume":"540","author":"Sapparapu","year":"2016","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"369ra179","DOI":"10.1126\/scitranslmed.aai8336","article-title":"Molecular determinants of human neutralizing antibodies isolated from a patientinfected with Zika virus","volume":"8","author":"Wang","year":"2016","journal-title":"Sci Trans Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"13679","DOI":"10.1038\/ncomms13679","article-title":"Neutralization mechanism of a highly potent antibody against Zika virus","volume":"7","author":"Zhang","year":"2016","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41594-017-0010-8","article-title":"Structural biology of Zika virus and other flaviviruses","volume":"25","author":"Hasan","year":"2018","journal-title":"NatStruct Mol Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.11.8475-8481.1997","article-title":"Proteolytic activation of tick-borne encephalitis virus by furin","volume":"71","author":"Stadler","year":"1997","journal-title":"J Virol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf5316","article-title":"The 3.8 A resolution cryo-EM structure of Zika virus","volume":"352","author":"Sirohi","year":"2016","journal-title":"Science"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2012.02.011","article-title":"Degrees of maturity: the complex structure and biology offlaviviruses","volume":"2","author":"Pierson","year":"2012","journal-title":"Curr Opin Virol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.245","article-title":"Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody","volume":"28","author":"Cherrier","year":"2009","journal-title":"EMBO J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2005.72.189","article-title":"Randomized, double-blind, phase III, pivotal field trial of the comparativeimmunogenicity, safety, and tolerability of two yellow fever 17D vaccines (Arilvax and YF-VAX) in healthy infants and children in Peru","volume":"72","author":"Belmusto-Worn","year":"2005","journal-title":"Am J Trop Med Hyg"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.08.024","article-title":"Field effectiveness of vaccination against tick-borne encephalitis","volume":"25","author":"Heinz","year":"2007","journal-title":"Vaccine"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1038\/s41467-019-09914-3","article-title":"Differential human antibody repertoires following Zika infection and the implicationsfor serodiagnostics and disease outcome","volume":"10","author":"Ravichandran","year":"2019","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.11.061","article-title":"Complement and its role in protection and pathogenesis of flavivirusinfections","volume":"26","author":"Avirutnan","year":"2008","journal-title":"Vaccine"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05859-11","article-title":"Poorly Neutralizing Cross-Reactive Antibodies against the Fusion Loop of West NileVirus Envelope Protein Protect In Vivo via Fc Receptor and Complement-Dependent Effector Mechanisms","volume":"85","author":"Vogt","year":"2011","journal-title":"J Virol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"14722","DOI":"10.1038\/ncomms14722","article-title":"A human antibody against Zika virus crosslinks the E protein to preventinfection","volume":"8","author":"Hasan","year":"2017","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature03956","article-title":"Structural basis of West Nile virus neutralization by a therapeuticantibody","volume":"437","author":"Nybakken","year":"2005","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"eaan6809","DOI":"10.1126\/sciimmunol.aan6809","article-title":"Zika virus activates de novo and cross-reactive memory B cell responses indengue-experienced donors","volume":"2","author":"Rogers","year":"2017","journal-title":"Sci Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.020","article-title":"Structural Basis of Zika Virus-Specific Antibody Protection","volume":"166","author":"Zhao","year":"2016","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.12.020","article-title":"Antibody-mediated neutralization of flaviviruses: A reductionist view","volume":"411","author":"Dowd","year":"2011","journal-title":"Virology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.03.002","article-title":"The Stoichiometry of Antibody-Mediated Neutralization and Enhancement of West NileVirus Infection","volume":"1","author":"Pierson","year":"2007","journal-title":"Cell Host Microbe"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800820","article-title":"Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy","volume":"379","author":"Sridhar","year":"2018","journal-title":"New Engl J Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by Zika virusinfection","volume":"353","author":"Stettler","year":"2016","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3644","DOI":"10.1038\/s41467-018-06006-6","article-title":"Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using machinelearning","volume":"9","author":"Dorigatti","year":"2018","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.05.059","article-title":"Modelling the immunological response to a tetravalent dengue vaccine from multiplephase-2 trials in Latin America and South East Asia","volume":"33","author":"Dorigatti","year":"2015","journal-title":"Vaccine"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.08.007","article-title":"The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity","volume":"8","author":"Beltramello","year":"2010","journal-title":"Cell Host Microbe"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.1205669","article-title":"A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins","volume":"333","author":"Corti","year":"2011","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nature06890","article-title":"Rapid cloning of high-affinity human monoclonal antibodies against influenzavirus","volume":"453","author":"Wrammert","year":"2008","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad6117","article-title":"Structural and molecular basis for Ebola virus neutralization by protective human antibodies","volume":"351","author":"Misasi","year":"2016","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.037","article-title":"Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protectionagainst Ebolaviruses","volume":"169","author":"Wec","year":"2017","journal-title":"Cell"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055515","article-title":"Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design","volume":"34","author":"Burton","year":"2016","journal-title":"Annu Rev Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/nri3516","article-title":"Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of thebeginning","volume":"13","author":"Kwong","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2492","article-title":"High-throughput sequencing of the paired human immunoglobulin heavy and light chainrepertoire","volume":"31","author":"DeKosky","year":"2013","journal-title":"Nat Biotechnol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/nm.3743","article-title":"In-depth determination and analysis of the human paired heavy- and light-chainantibody repertoire","volume":"21","author":"DeKosky","year":"2015","journal-title":"Nat Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.024","article-title":"Ultra-high-throughput sequencing of the immune receptor repertoire from millions oflymphocytes","volume":"11","author":"McDaniel","year":"2016","journal-title":"Nat Protoc"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4052","article-title":"Functional interrogation and mining of natively paired human VH:VL antibodyrepertoires","volume":"36","author":"Wang","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525510113","article-title":"Large-scale sequence and structural comparisons of human naive andantigen-experienced antibody repertoires","volume":"113","author":"DeKosky","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2019.01.020","article-title":"Ultrasonically-guided flow focusing generates precise emulsion droplets forhigh-throughput single cell analyses","volume":"128","author":"Lagerman","year":"2019","journal-title":"J Biosci Bioeng"},{"key":"B45","doi-asserted-by":"publisher","first-page":"S0264410X19307030","DOI":"10.1016\/j.vaccine.2019.05.066","article-title":"Purification of flavivirus VLPs by a two-step chomatographic process","volume":"37","author":"Lima","year":"2019","journal-title":"Vaccine"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.04.077","article-title":"Purification of yellow fever virus produced in Vero cells for inactivated vaccine manufacture","volume":"37","author":"Pato","year":"2019","journal-title":"Vaccine"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2214","article-title":"Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing","volume":"30","author":"Whitehead","year":"2012","journal-title":"Nat Biotechnol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt382","article-title":"IgBLAST: an immunoglobulin variable domain sequence analysis tool","volume":"41","author":"Ye","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e2584","DOI":"10.7717\/peerj.2584","article-title":"VSEARCH: a versatile open source tool for metagenomics","volume":"4","author":"Rognes","year":"2016","journal-title":"Peer J"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and clustering orders of magnitude faster than BLAST","volume":"26","author":"Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"B51","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/978-1-4939-0348-1_6","article-title":"Pseudo-infectious Reporter Virus Particles for Measuring Antibody-Mediated Neutralization and Enhancement of Dengue Virus Infection","volume-title":"Dengue","author":"Mukherjee","year":"2014"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01140-14","article-title":"Combined Effects of the Structural Heterogeneity and Dynamics of Flaviviruses on Antibody Recognition","volume":"88","author":"Dowd","year":"2014","journal-title":"J Virol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.07.049","article-title":"Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype","volume":"16","author":"Dowd","year":"2016","journal-title":"Cell Rep"},{"key":"B54","volume-title":"A language and environment for statistical computing. R Foundation for Statistical Computing","year":"2019"},{"key":"B55","volume-title":"RStudio: Integrated Development Environment for R","year":"2016"},{"key":"B56","doi-asserted-by":"crossref","first-page":"260 p","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: elegant graphics for data analysis","author":"Wickham","year":"2016"},{"key":"B57","article-title":"Cryo-EM Structure of Immature Zika Virus (:unav)","volume-title":"Nat Struct Mol Biol","author":"Mangala Prasad","year":"2017"},{"key":"B58","article-title":"The cryo-EM structure of Zika Virus. (:unav)","volume-title":"Science","author":"Sirohi","year":"2016"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2020.06.011","article-title":"The covalent SNAP tag for protein display quantification and low-pH protein engineering","volume":"320","author":"Jin","year":"2020","journal-title":"J Biotechnol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.09.025","article-title":"SORTCERY\u2014A High\u2013Throughput Method to Affinity Rank Peptide Ligands","volume":"427","author":"\u201cLuther","year":"2015","journal-title":"J Mol Biol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"eaap8029","DOI":"10.1126\/sciimmunol.aap8029","article-title":"Clonal selection drives protective memory B cell responses in controlled human malaria infection","volume":"3","author":"Murugan","year":"2018","journal-title":"Sci Immunol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.cell.2017.04.024","article-title":"Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico","volume":"169","author":"Robbiani","year":"2017","journal-title":"Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e23156","DOI":"10.7554\/eLife.23156","article-title":"Measuring the sequence-affinity landscape of antibodies with massively parallel titration curves","volume":"5","author":"Adams","year":"2016","journal-title":"eLife"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1101\/2020.06.17.157982","article-title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","volume":"182","author":"Starr","year":"2020","journal-title":"Microbiology"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.012","article-title":"Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies","volume":"37","author":"Kwong","year":"2012","journal-title":"Immunity"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3058","article-title":"A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus","volume":"16","author":"Dejnirattisai","year":"2015","journal-title":"Nat Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nature14130","article-title":"Recognition determinants of broadly neutralizing human antibodies against dengue viruses","volume":"520","author":"Rouvinski","year":"2015","journal-title":"Nature"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.615102\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T04:55:40Z","timestamp":1614142540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.615102\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":67,"alternative-id":["10.3389\/fimmu.2021.615102"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.615102","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]},"article-number":"615102"}}