{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:55:07Z","timestamp":1790110507752,"version":"4.0.1"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"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>Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longitudinally across four time points over the period of six months in Peru and over two time points in travelers. We show that epitopes eliciting the strongest flavivirus cross-reactive antibodies, in both primary and secondary infections were concentrated in the capsid, E, NS1, NS3 and NS5 proteins. The IgG antibody responses against NS1 and NS3 followed a rise-and-fall pattern, with peak titers between two to four weeks after onset of illness. The response to the E and NS5 proteins increased rapidly in the acute phase and was maintained at stable levels until at least 6 months after illness. A more scattered IgM antibody reactivity across the viral proteome was observed in the acute phase of the disease and that persisted through the 6-month window. The magnitude, breadth (i.e. number of unique epitopes targeted) and depth (i.e. number of epitope variants recognized) of the IgG response was higher in secondary infections compared to primary infections. For IgM antibodies, the magnitude of the response was higher in primary infected individuals whereas the breadth and depth of the response was lower in this group compared with the endemic subjects. Finally, through this arboviral proteome-wide epitope mapping, we were able to identify IgM and IgG dengue-specific epitopes which can be useful serological markers for dengue diagnosis and serostatus determination.<\/jats:p>","DOI":"10.3389\/fimmu.2021.686691","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T06:46:11Z","timestamp":1625467571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Francesca","family":"Falconi-Agapito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kerkhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiomara","family":"Merino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Michiels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Van Esbroeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Bartholomeeusen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Talledo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin K.","family":"Ari\u00ebn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32560-1","article-title":"Dengue","volume":"393","author":"Wilder-Smith","year":"2019","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000787","article-title":"Arboviral Etiologies of Acute Febrile Illnesses in Western South America, 2000-2007","volume":"4","author":"Forshey","year":"2010","journal-title":"PloS Negl Trop Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2009.02.003","article-title":"Molecular Evolution of Dengue Viruses: Contributions of Phylogenetics to Understanding the History and Epidemiology of the Preeminent Arboviral Disease","volume":"9","author":"Weaver","year":"2009","journal-title":"Infect Genet Evol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6836","article-title":"Antibody-Dependent Enhancement of Severe Dengue Disease in Humans","volume":"358","author":"Katzelnick","year":"2017","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-013-1645-3","article-title":"Secondary Infection as a Risk Factor for Dengue Hemorrhagic Fever\/Dengue Shock Syndrome: An Historical Perspective and Role of Antibody-Dependent Enhancement of Infection","volume":"158","author":"Guzman","year":"2013","journal-title":"Arch Virol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.coviro.2020.08.006","article-title":"Protective and Enhancing Interactions Among Dengue Viruses 1-4 and Zika Virus","volume":"43","author":"Katzelnick","year":"2020","journal-title":"Curr Opin Virol"},{"key":"B7","article-title":"Observations Related to Pathogensis of Dengue Hemorrhagic Fever. VI. Hypotheses and Discussion","volume":"42","author":"Halstead","year":"1970","journal-title":"Yale J Biol Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e1007640","DOI":"10.1371\/journal.ppat.1007640","article-title":"The Possible Role of Cross-Reactive Dengue Virus Antibodies in Zika Virus Pathogenesis","volume":"15","author":"Langerak","year":"2019","journal-title":"PloS Pathog"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00334","article-title":"Cross-Reactive Immunity Among Flaviviruses","volume":"11","author":"Rathore","year":"2020","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix972","article-title":"Arbovirus Diagnostics: From Bad to Worse Due to Expanding Dengue Virus Vaccination and Zika Virus Epidemics","volume":"66","author":"Simmons","year":"2018","journal-title":"Clin Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal4365","article-title":"Enhancement of Zika Virus Pathogenesis by Preexisting Antiflavivirus Immunity","volume":"356","author":"Bardina","year":"2017","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-020-00389-2","article-title":"Enhancement of Zika Virus Infection by Antibodies From West Nile Virus Seropositive Individuals With No History of Clinical Infection","volume":"22","author":"Garg","year":"2021","journal-title":"BMC Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e190098","DOI":"10.1590\/0074-02760190098","article-title":"Previous Dengue or Zika Virus Exposure Can Drive to Infection Enhancement or Neutralisation of Other Flaviviruses","volume":"114","author":"Oliveira","year":"2019","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B14","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":"N Engl J Med"},{"key":"B15","unstructured":"Background Paper on Dengue Vaccines. In World Health Organization2018"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(18)30295-X","article-title":"Dengue Vaccine: Reliably Determining Previous Exposure","volume":"6","author":"Ari\u00ebn","year":"2018","journal-title":"Lancet Glob Heal"},{"key":"B17","doi-asserted-by":"publisher","first-page":"20190234","DOI":"10.1098\/rsif.2019.0234","article-title":"Serostatus Testing and Dengue Vaccine Cost-Benefit Thresholds","volume":"16","author":"Pearson","year":"2019","journal-title":"J R Soc Interface"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.04.011","article-title":"Arboviruses: A Global Public Health Threat","volume":"38","author":"Girard","year":"2020","journal-title":"Vaccine"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30722-2","article-title":"Optimising Dengue Pre-Vaccination Screening","volume":"21","author":"Wilder-Smith","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"B20","unstructured":"Reported Cases of Dengue Fever in the Americas, by Country or Territory. In Pan American Health Organization2020"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e88","DOI":"10.1016\/S1473-3099(16)30473-X","article-title":"Dengue: Knowledge Gaps, Unmet Needs, and Research Priorities","volume":"17","author":"Katzelnick","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2459","article-title":"Evaluation of Diagnostic Tests: Dengue","volume":"8","author":"Peeling","year":"2010","journal-title":"Nat Rev Microbiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.03.005","article-title":"Analysis of Specific IgM Responses in Secondary Dengue Virus Infections: Levels and Positive Rates in Comparison With Primary Infections","volume":"31","author":"Chanama","year":"2004","journal-title":"J Clin Virol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03203-15","article-title":"B Cell Responses During Secondary Dengue Virus Infection Are Dominated by Highly Cross-Reactive, Memory-Derived Plasmablasts","volume":"90","author":"Priyamvada","year":"2016","journal-title":"J Virol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2019.11.005","article-title":"Reliable Serological Diagnostic Tests for Arboviruses: Feasible or Utopia","volume":"28","author":"Kerkhof","year":"2020","journal-title":"Trends Microbiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704984114","article-title":"Antibody-Based Assay Discriminates Zika Virus Infection From Other Flaviviruses","volume":"114","author":"Balmaseda","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e0007649","DOI":"10.1371\/journal.pntd.0007649","article-title":"A High-Throughput and Multiplex Microsphere Immunoassay Based on non-Structural Protein 1 Can Discriminate Three Flavivirus Infections","volume":"13","author":"Tyson","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e0244601","DOI":"10.1371\/journal.pone.0244601","article-title":"Evaluation of Eight Commercial Zika Virus IgM and IgG Serology Assays for Diagnostics and Research","volume":"16","author":"Low","year":"2021","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003171","article-title":"Evaluation of Commercially Available Diagnostic Tests for the Detection of Dengue Virus NS1 Antigen and Anti-Dengue Virus IgM Antibody","volume":"8","author":"Hunsperger","year":"2014","journal-title":"PloS Negl Trop Dis"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/s0065-3527(03)61001-8","article-title":"Serodiagnosis of Flaviviral Infections and Vaccinations in Humans","volume":"61","author":"Kuno","year":"2003","journal-title":"Adv Virus Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/mBio.00095-18","article-title":"Diagnosis of Zika Virus Infection by Peptide Array and ELISA","volume":"9","author":"Mishra","year":"2018","journal-title":"MBio"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700029","article-title":"Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections","volume":"198","author":"Hertz","year":"2017","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"100189","DOI":"10.1016\/j.xcrm.2020.100189","article-title":"Epitope-Resolved Profiling of the SARS-CoV-2 Antibody Response Identifies Cross-Reactivity With an Endemic Human Coronaviruses","volume":"2","author":"Ladner","year":"2021","journal-title":"Cell Reports Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3581","DOI":"10.1038\/s41467-020-17488-8","article-title":"SARS-CoV-2 Proteome Microarray for Global Profiling of COVID-19 Specific IgG and IgM Responses","volume":"11","author":"Jiang","year":"2020","journal-title":"Nat Commun"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2009.02.010","article-title":"Development and Validation of Real-Time One-Step Reverse Transcription-PCR for the Detection and Typing of Dengue Viruses","volume":"45","author":"Leparc-Goffart","year":"2009","journal-title":"J Clin Virol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.10.4977","article-title":"Serotype-Specific Detection of Dengue Viruses in a Fourplex Real-Time Reverse Transcriptase PCR Assay","volume":"43","author":"Johnson","year":"2005","journal-title":"J Clin Microbiol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002311","article-title":"Analytical and Clinical Performance of the CDC Real Time RT-PCR Assay for Detection and Typing of Dengue Virus","volume":"7","author":"Santiago","year":"2013","journal-title":"PloS Negl Trop Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.04.087","article-title":"A New Genetic Variant of Dengue Serotype 2 Virus Circulating in the Peruvian Amazon","volume":"96","author":"Falconi-Agapito","year":"2020","journal-title":"Int J Infect Dis"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e0007047","DOI":"10.1371\/journal.pntd.0007047","article-title":"Dengue and Chikungunya Among Outpatients With Acute Undifferentiated Fever in Kinshasa, Democratic Republic of Congo: A Cross-Sectional Study","volume":"13","author":"Proesmans","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-019-03472-8","article-title":"Challenges in Diagnosing Zika\u2014Experiences From a Reference Laboratory in a Non-Endemic Setting","volume":"38","author":"Van den Bossche","year":"2019","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0210-3","article-title":"The Immune Response Against Flaviviruses","volume":"19","author":"Slon Campos","year":"2018","journal-title":"Nat Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118964","article-title":"Dominant Recognition by Human CD8+ Cytotoxic T Lymphocytes of Dengue Virus Nonstructural Proteins NS3 and NS1.2a","volume":"98","author":"Mathew","year":"1996","journal-title":"J Clin Invest"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00678.x","article-title":"Understanding the Contribution of Cellular Immunity to Dengue Disease Pathogenesis","volume":"225","author":"Mathew","year":"2008","journal-title":"Immunol Rev"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, Cross-Reactivity, and Function of Antibodies Elicited by Zika Virus Infection","volume":"353","author":"Stettler","year":"2016","journal-title":"Sci (80-)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix967","article-title":"Virus and Antibody Dynamics in Travelers With Acute Zika Virus Infection","volume":"66","author":"Barzon","year":"2018","journal-title":"Clin Infect Dis"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.05425-11","article-title":"Estimation of Dengue Virus IgM Persistence Using Regression Analysis","volume":"18","author":"Prince","year":"2011","journal-title":"Clin Vaccine Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jcv.2017.05.001","article-title":"Re-Evaluation of Routine Dengue Virus Serology in Travelers in the Era of Zika Virus Emergence","volume":"92","author":"van Meer","year":"2017","journal-title":"J Clin Virol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-13-302","article-title":"Cross-Reactivities Between Human IgMs and the Four Serotypes of Dengue Virus as Probed With Artificial Homodimers of Domain-III From the Envelope Proteins","volume":"13","author":"Zidane","year":"2013","journal-title":"BMC Infect Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.7.5.774-777.2000","article-title":"Serotype-Cross-Reactive Immunoglobulin M Responses in Dengue Virus Infections Determined by Enzyme-Linked Immunosorbent Assay","volume":"7","author":"Nawa","year":"2000","journal-title":"Clin Diagn Lab Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12879-018-3058-0","article-title":"Prolonged Persistence of IgM Against Dengue Virus Detected by Commonly Used Commercial Assays","volume":"18","author":"Chien","year":"2018","journal-title":"BMC Infect Dis"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01205-17","article-title":"Analysis of Individuals From a Dengue-Endemic Region Helps Define the Footprint and Repertoire of Antibodies Targeting Dengue Virus 3 Type-Specific Epitopes","volume":"8","author":"Andrade","year":"2017","journal-title":"MBio"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.65.4.1823-1828.1991","article-title":"Dengue Virus-Specific, Human CD4+ CD8- Cytotoxic T-Cell Clones: Multiple Patterns of Virus Cross-Reactivity Recognized by NS3-Specific T-Cell Clones","volume":"65","author":"Kurane","year":"1991","journal-title":"J Virol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02125","article-title":"Human T Cell Response to Dengue Virus Infection","volume":"10","author":"Tian","year":"2019","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010867107","article-title":"Immunodominant T-Cell Responses to Dengue Virus NS3 Are Associated With DHF","volume":"107","author":"Duangchinda","year":"2010","journal-title":"Proc Natl Acad Sci"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1126\/science.1185181","article-title":"Cross-Reacting Antibodies Enhance Dengue Virus Infection in Humans","volume":"328","author":"Dejnirattisai","year":"2010","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","first-page":"e1004386","DOI":"10.1371\/journal.ppat.1004386","article-title":"Dengue Viruses Are Enhanced by Distinct Populations of Serotype Cross-Reactive Antibodies in Human Immune Sera","volume":"10","author":"de Alwis","year":"2014","journal-title":"PloS Pathog"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15411","article-title":"Covalently Linked Dengue Virus Envelope Glycoprotein Dimers Reduce Exposure of the Immunodominant Fusion Loop Epitope","volume":"8","author":"Rouvinski","year":"2017","journal-title":"Nat Commun"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900093","article-title":"Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody","volume":"183","author":"Sultana","year":"2009","journal-title":"J Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.2.1223-1231.2005","article-title":"Variable Surface Epitopes in the Crystal Structure of Dengue Virus Type 3 Envelope Glycoprotein","volume":"79","author":"Modis","year":"2005","journal-title":"J Virol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9200","article-title":"Monoclonal Antibody Mapping of the Envelope Glycoprotein of the Dengue 2 Virus, Jamaica","volume":"246","author":"Roehrig","year":"1998","journal-title":"Virology"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.13242\/j.cnki.bingduxuebao.002828","article-title":"Mapping of the B Cell Neutralizing Epitopes on ED III of Envelope Protein From Dengue Virus","volume":"31","author":"Lin","year":"2015","journal-title":"Chin J Virol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/BF01309478","article-title":"Precise Location of Sequential Dengue Virus Subcomplex and Complex B Cell Epitopes on the Nonstructural-1 Glycoprotein","volume":"137","author":"Falconar","year":"1994","journal-title":"Arch Virol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.12.010","article-title":"Comprehensive Mapping of Immunodominant and Conserved Serotype- and Group-Specific B-Cell Epitopes of Nonstructural Protein 1 From Dengue Virus Type 1","volume":"398","author":"Chen","year":"2010","journal-title":"Virology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"6975","DOI":"10.1038\/s41598-017-07308-3","article-title":"Antibodies Against Modified NS1 Wing Domain Peptide Protect Against Dengue Virus Infection","volume":"7","author":"Lai","year":"2017","journal-title":"Sci Rep"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1066#","article-title":"Novel Differential Linear B-Cell Epitopes to Identify Zika and Dengue Virus Infections in Patients","volume":"8","author":"Amrun","year":"2019","journal-title":"Clin Transl Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.11.006","article-title":"Quantification of the Epitope Diversity of HIV-1-Specific Binding Antibodies by Peptide Microarrays for Global HIV-1 Vaccine Development","volume":"416","author":"Stephenson","year":"2015","journal-title":"J Immunol Methods"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.686691\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T06:46:19Z","timestamp":1625467579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.686691\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":66,"alternative-id":["10.3389\/fimmu.2021.686691"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.686691","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]},"article-number":"686691"}}