{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:41:04Z","timestamp":1765280464796,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The George Washington University School of Medicine and Health Sciences","award":["UL1TR001876","KL2TR001877"],"award-info":[{"award-number":["UL1TR001876","KL2TR001877"]}]},{"name":"NIH National Center for Advancing Translational Sciences","award":["UL1TR001876","KL2TR001877"],"award-info":[{"award-number":["UL1TR001876","KL2TR001877"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The Zika virus (ZIKV) was responsible for a major outbreak in 2015 in the Americas. Infections were associated with increased cases of microcephaly in infants and Guillain\u2013Barr\u00e9 Syndrome (GBS) in adults. Our group previously demonstrated that Zika-associated GBS correlated with the increased neutralization of ZIKV and DENV2, but the antibody specificity was not analyzed. Here, we generated reporter virus particles (RVPs) of ZIKV with specific-point mutations that allowed us to investigate the specificity of circulating plasma antibodies at two different timepoints from individuals with Zika-associated GBS. We found that neutralizing antibody titers to ZIKV waned between one and two years post-ZIKV infection in GBS-negative but not GBS-positive individuals. Interestingly, plasma neutralization by GBS-negative individuals was more sensitive to a mutation at position N154A than plasma from GBS-positive individuals. To determine if waning was associated with different levels of B-cell activation at the time of infection, pro-inflammatory cytokines were measured, but no differences were observed in people with or without GBS. These data suggest subtle differences between GBS-positive and-negative individuals\u2019 circulating antibodies, where antibodies from GBS-positive individuals may target different epitopes and remain in circulation longer as compared to GBS-negative individuals.<\/jats:p>","DOI":"10.3390\/v16111704","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:11:24Z","timestamp":1730279484000},"page":"1704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of Memory Antibody Responses in Individuals with Zika-Associated Guillain\u2013Barr\u00e9 Syndrome"],"prefix":"10.3390","volume":"16","author":[{"given":"Michelle","family":"Premazzi Papa","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Mantus","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1955-5239","authenticated-orcid":false,"given":"Kareem","family":"Kabra","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Herrera Gomez","sequence":"additional","affiliation":[{"name":"Department of Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Encinales","sequence":"additional","affiliation":[{"name":"Allied Research Society Colombia, Barranquilla 080020, Atl\u00e1ntico, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres","family":"Cadena","sequence":"additional","affiliation":[{"name":"Cl\u00ednica de la Costa SAS, Barranquilla 080020, Atl\u00e1ntico, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-9867","authenticated-orcid":false,"given":"Aileen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"},{"name":"Department of Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-8073","authenticated-orcid":false,"given":"Rebecca M.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1126\/science.aaf5036","article-title":"Zika virus in the Americas: Early epidemiological and genetic findings","volume":"352","author":"Faria","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s12985-021-01611-2","article-title":"The key amino acids of E protein involved in early flavivirus infection: Viral entry","volume":"18","author":"Hu","year":"2021","journal-title":"Virol. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1074\/mcp.R116.065649","article-title":"Protein Interactions during the Flavivirus and Hepacivirus Life Cycle","volume":"16","author":"Gerold","year":"2017","journal-title":"Mol. Cell. Proteom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-med-040717-051127","article-title":"Zika Virus Vaccine Development: Progress in the Face of New Challenges","volume":"70","author":"Diamond","year":"2019","journal-title":"Annu. Rev. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.aaf5316","article-title":"The 3.8 \u00c5 resolution cryo-EM structure of Zika virus","volume":"352","author":"Sirohi","year":"2016","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dussupt, V., Modjarrad, K., and Krebs, S.J. (2020). Landscape of Monoclonal Antibodies Targeting Zika and Dengue: Therapeutic Solutions and Critical Insights for Vaccine Development. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.621043"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Deng, Y.-Q., Dai, J.-X., Ji, G.-H., Jiang, T., Wang, H.-J., Yang, H.-O., Tan, W.-L., Liu, R., Yu, M., and Ge, B.-X. (2011). A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016059"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1016","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":"ref_9","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nature18938","article-title":"Structural basis of potent Zika\u2013dengue virus antibody cross-neutralization","volume":"536","author":"Dejnirattisai","year":"2016","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","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":"ref_11","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1056\/NEJMp1602708","article-title":"Zika Virus as a Cause of Neurologic Disorders","volume":"374","author":"Broutet","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/uog.15831","article-title":"Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: Tip of the iceberg?","volume":"47","author":"Malinger","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0140-6736(16)00339-1","article-title":"Guillain-Barr\u00e9 syndrome","volume":"388","author":"Willison","year":"2016","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00431-006-0140-1","article-title":"Infections and vaccinations preceding childhood Guillain-Barr\u00e9 syndrome: A prospective study","volume":"165","author":"Schessl","year":"2006","journal-title":"Eur. J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e575","DOI":"10.1212\/NXI.0000000000000575","article-title":"Guillain-Barr\u00e9 syndrome and related diseases after influenza virus infection","volume":"6","author":"Yamana","year":"2019","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/S0140-6736(16)00562-6","article-title":"Guillain-Barr\u00e9 Syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study","volume":"387","author":"Blake","year":"2016","journal-title":"Lancet"},{"key":"ref_17","unstructured":"World Health Organization (2016). Situation Report: Zika virus, Microcephaly, Guillain-Barr\u00e9 Syndrome, World Health Organization. Available online: https:\/\/iris.who.int\/handle\/10665\/250633."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1056\/NEJMoa1605564","article-title":"Guillain\u2013Barr\u00e9 Syndrome Associated with Zika Virus Infection in Colombia","volume":"375","author":"Parra","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e20210580","DOI":"10.1084\/jem.20210580","article-title":"The immunodominant antibody response to Zika virus NS1 protein is characterized by cross-reactivity to self","volume":"218","author":"Cavazzoni","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/infdis\/jiy466","article-title":"Augmented Zika and Dengue Neutralizing Antibodies Are Associated with Guillain-Barr\u00e9 Syndrome","volume":"219","author":"Lynch","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41426-018-0151-9","article-title":"Long-term clinical outcomes of Zika-associated Guillain-Barr\u00e9 syndrome","volume":"7","author":"Chang","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1093\/infdis\/jiy164","article-title":"Longitudinal Analysis of Antibody Cross-neutralization Following Zika Virus and Dengue Virus Infection in Asia and the Americas","volume":"218","author":"Montoya","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_23","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":"1138","author":"Mukherjee","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gutierrez-Barbosa, H., Medina-Moreno, S., Zapata, J.C., and Chua, J.V. (2020). Dengue Infections in Colombia: Epidemiological Trends of a Hyperendemic Country. Trop. Med. Infect. Dis., 5.","DOI":"10.3390\/tropicalmed5040156"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7007","DOI":"10.1073\/pnas.91.15.7007","article-title":"Tumor necrosis factor alpha is an autocrine growth factor for normal human B cells","volume":"91","author":"Boussiotis","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1136\/gut.2003.026278","article-title":"The CD40\/CD40L costimulatory pathway in inflammatory bowel disease","volume":"53","author":"Danese","year":"2004","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.4049\/jimmunol.0803009","article-title":"IL-21: An Executor of B Cell Fate1","volume":"182","author":"Konforte","year":"2009","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nemmer, J.M., Kuchner, M., Datsi, A., Ol\u00e1h, P., Julia, V., Raap, U., and Homey, B. (2021). Interleukin-31 Signaling Bridges the Gap Between Immune Cells, the Nervous System and Epithelial Tissues. Front. Med., 8.","DOI":"10.3389\/fmed.2021.639097"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.4049\/jimmunol.1900408","article-title":"IL-33 Is a Cell-Intrinsic Regulator of Fitness during Early B Cell Development","volume":"203","author":"Stier","year":"2019","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.4049\/jimmunol.1502641","article-title":"IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity","volume":"197","author":"Subbarayal","year":"2016","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cyto.2015.02.007","article-title":"B cells responses and cytokine production are regulated by their immune microenvironment","volume":"74","author":"Vazquez","year":"2015","journal-title":"Cytokine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112942","DOI":"10.1016\/j.celrep.2023.112942","article-title":"Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes","volume":"42","author":"Sankhala","year":"2023","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","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 Flavivirus Broadly Protective Antibody","volume":"19","author":"Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e01485-19","DOI":"10.1128\/mBio.01485-19","article-title":"Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies","volume":"10","author":"Gallichotte","year":"2019","journal-title":"mBio"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0022-510X(91)90313-V","article-title":"Comparative analysis of cytokine patterns in immunological, infectious, and oncological neurological disorders","volume":"104","author":"Weller","year":"1991","journal-title":"J. Neurol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Langerak, T., Mumtaz, N., Tolk, V.I., van Gorp, E.C.M., Martina, B.E., Rockx, B., and Koopmans, M.P.G. (2019). The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007640"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.00113-19","article-title":"Envelope Protein Glycosylation Mediates Zika Virus Pathogenesis","volume":"93","author":"Carbaugh","year":"2019","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.virol.2017.12.032","article-title":"The Zika virus envelope protein glycan loop regulates virion antigenicity","volume":"515","author":"Goo","year":"2018","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/ni.3849","article-title":"Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection","volume":"18","author":"Fernandez","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","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":"ref_41","doi-asserted-by":"crossref","first-page":"823","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":"Science"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/11\/1704\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:24:16Z","timestamp":1760113456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/11\/1704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["v16111704"],"URL":"https:\/\/doi.org\/10.3390\/v16111704","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2024,10,30]]}}}