{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:56:08Z","timestamp":1789797368090,"version":"4.0.1"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ-03081-17, APQ-04295-17 and RED-00282-16"],"award-info":[{"award-number":["APQ-03081-17, APQ-04295-17 and RED-00282-16"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["402256\/2022-0"],"award-info":[{"award-number":["402256\/2022-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior \u2013 Brasil","doi-asserted-by":"crossref","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Zika virus (ZIKV), an arbovirus from the <jats:italic>Flaviviridae<\/jats:italic> family, is the causative agent of Zika fever, a mild and frequent oligosymptomatic disease in humans. Nonetheless, on rare occasions, ZIKV infection can be associated with Guillain-Barr\u00e9 Syndrome (GBS), and severe congenital complications, such as microcephaly. The oligosymptomatic disease, however, presents symptoms that are quite similar to those observed in infections caused by other frequent co-circulating arboviruses, including dengue virus (DENV). Moreover, the antigenic similarity between ZIKV and DENV, and even with other members of the <jats:italic>Flaviviridae<\/jats:italic> family, complicates serological testing due to the high cross-reactivity of antibodies. Here, we designed, produced in a prokaryotic expression system, and purified three multiepitope proteins (ZIKV-1, ZIKV-2, and ZIKV-3) for differential diagnosis of Zika. The proteins were evaluated as antigens in ELISA tests for the detection of anti-ZIKV IgG using ZIKV- and DENV-positive human sera. The recombinant proteins were able to bind and detect anti-ZIKV antibodies without cross-reactivity with DENV-positive sera and showed no reactivity with Chikungunya virus (CHIKV)- positive sera. ZIKV-1, ZIKV-2, and ZIKV-3 proteins presented 81.6%, 95%, and 66% sensitivity and 97%, 96%, and 84% specificity, respectively. Our results demonstrate the potential of the designed and expressed antigens in the development of specific diagnostic tests for the detection of IgG antibodies against ZIKV, especially in regions with the circulation of multiple arboviruses.<\/jats:p>","DOI":"10.1371\/journal.pntd.0012100","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T17:42:52Z","timestamp":1713462172000},"page":"e0012100","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Design, development, and validation of multi-epitope proteins for serological diagnosis of Zika virus infections and discrimination from dengue virus seropositivity"],"prefix":"10.1371","volume":"18","author":[{"given":"Samille Henriques","family":"Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus","family":"S\u00e1 Magalh\u00e3es Serafim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00eds de F\u00e1tima Silva","family":"Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia","family":"Zini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f4natas Santos","family":"Abrah\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maur\u00edcio Lacerda","family":"Nogueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordana Grazziela Alves","family":"Coelho dos Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via Fonseca","family":"Bagno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1416-8694","authenticated-orcid":true,"given":"Fl\u00e1vio Guimar\u00e3es","family":"da Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"issue":"5","key":"pntd.0012100.ref001","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus. 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Isolations and serological specificity","volume":"46","author":"GWA DICK","year":"1952","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"6283","key":"pntd.0012100.ref002","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":"NR Faria","year":"2016","journal-title":"Science"},{"issue":"7","key":"pntd.0012100.ref003","doi-asserted-by":"crossref","first-page":"e0235010","DOI":"10.1371\/journal.pone.0235010","article-title":"Zika epidemic and microcephaly in Brazil: Challenges for access to health care and promotion in three epidemic areas.","volume":"15","author":"PC Peiter","year":"2020","journal-title":"PLoS One."},{"issue":"8\u20139","key":"pntd.0012100.ref004","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.micinf.2019.04.005","article-title":"Zika virus infection: an update","volume":"21","author":"P Ferraris","year":"2019","journal-title":"Microbes Infect"},{"key":"pntd.0012100.ref005","volume":"54","author":"Secret\u00e1ria de Vigil\u00e2ncia em Sa\u00fade e Ambiente\u2014Minist\u00e9rio da Sa\u00fade do Brasil.","year":"2023","journal-title":"Boletim Epidemiol\u00f3gico 1."},{"key":"pntd.0012100.ref006","first-page":"54","year":"2023","journal-title":"Secret\u00e1ria de Vigil\u00e2ncia em Sa\u00fade e Ambiente\u2014Minist\u00e9rio da Sa\u00fade do Brasil. No Title. Bol Epidemiol 5"},{"key":"pntd.0012100.ref007","author":"Center for Disease Control and Prevention (CDC)","year":"2019","journal-title":"Zika virus"},{"issue":"4","key":"pntd.0012100.ref008","doi-asserted-by":"crossref","first-page":"316","DOI":"10.4103\/jispcd.JISPCD_433_18","article-title":"Zika Virus: A Global Public Health Menace: A Comprehensive Update.","volume":"9","author":"S Hasan","year":"2019","journal-title":"J Int Soc Prev Community Dent"},{"issue":"18","key":"pntd.0012100.ref009","doi-asserted-by":"crossref","first-page":"475","DOI":"10.15585\/mmwr.mm6518e2","article-title":"Comparison of Test Results for Zika Virus RNA in Urine, Serum, and Saliva Specimens from Persons with Travel-Associated Zika Virus Disease\u2014Florida, 2016.","volume":"65","author":"AM Bingham","year":"2016","journal-title":"MMWR Morb Mortal Wkly 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Distinguish Zika and Dengue Virus Infections","volume":"24","author":"W-Y Tsai","year":"2018","journal-title":"Emerg Infect Dis"},{"issue":"2","key":"pntd.0012100.ref030","doi-asserted-by":"crossref","first-page":"e0004517","DOI":"10.1371\/journal.pntd.0004517","article-title":"Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise.","volume":"10","author":"M Sarno","year":"2016","journal-title":"PLoS Negl Trop Dis."},{"key":"pntd.0012100.ref031","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijbiomac.2021.12.196","article-title":"New insights into the recombinant proteins and monoclonal antibodies employed to immunodiagnosis and control of Zika virus infection: A review","volume":"200","author":"ICL Magalh\u00e3es","year":"2022","journal-title":"Int J Biol Macromol"},{"issue":"8","key":"pntd.0012100.ref032","doi-asserted-by":"crossref","first-page":"e1007766","DOI":"10.1371\/journal.ppat.1007766","article-title":"Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques.","volume":"15","author":"ME Breitbach","year":"2019","journal-title":"PLoS Pathog."},{"key":"pntd.0012100.ref033","author":"Secret\u00e1ria de Vigil\u00e2ncia em Sa\u00fade e Ambiente\u2014Minist\u00e9rio da Sa\u00fade do Brasil.","year":"2024","journal-title":"No Title. 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Dis"},{"issue":"1","key":"pntd.0012100.ref037","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12978-017-0285-6","article-title":"Zika virus infection in pregnancy: a systematic review of disease course and complications.","volume":"14","author":"EC Chibueze","year":"2017","journal-title":"Reprod Health."},{"key":"pntd.0012100.ref038","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ejogrb.2021.07.012","article-title":"Zika virus infection in pregnant women and their children: A review.","volume":"265","author":"E Marb\u00e1n-Castro","year":"2021","journal-title":"Eur J Obstet Gynecol Reprod Biol."},{"issue":"8","key":"pntd.0012100.ref039","doi-asserted-by":"crossref","first-page":"574","DOI":"10.2471\/BLT.16.171207","article-title":"Background review for diagnostic test development for Zika virus infection","volume":"94","author":"RN Charrel","year":"2016","journal-title":"Bull World Health 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Immunol"},{"key":"pntd.0012100.ref050","doi-asserted-by":"crossref","first-page":"884701","DOI":"10.3389\/fpubh.2022.884701","article-title":"Multi-Epitope Protein as a Tool of Serological Diagnostic Development for HTLV-1 and HTLV-2 Infections.","volume":"10","author":"M Franco G de","year":"2022","journal-title":"Front public Heal."},{"issue":"8","key":"pntd.0012100.ref051","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.14202\/vetworld.2021.2187-2196","article-title":"Evaluation of chimeric proteins for serological diagnosis of brucellosis in cattle","volume":"14","author":"AK Bulashev","year":"2021","journal-title":"Vet world"},{"issue":"18","key":"pntd.0012100.ref052","doi-asserted-by":"crossref","first-page":"6805","DOI":"10.1007\/s00253-021-11518-1","article-title":"Development of a chimeric protein based on a proteomic approach for the serological diagnosis of human tegumentary leishmaniasis","volume":"105","author":"GC Garcia","year":"2021","journal-title":"Appl 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