{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:32:16Z","timestamp":1789061536962,"version":"build-2803163510"},"reference-count":122,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88882.379743\/2019-01"],"award-info":[{"award-number":["88882.379743\/2019-01"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006162","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Ci\u00eancia e Tecnologia de Pernambuco","doi-asserted-by":"publisher","award":["APQ-01482-2.02\/22"],"award-info":[{"award-number":["APQ-01482-2.02\/22"]}],"id":[{"id":"10.13039\/501100006162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006162","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Ci\u00eancia e Tecnologia de Pernambuco","doi-asserted-by":"publisher","award":["APQ-1859-2.02\/24"],"award-info":[{"award-number":["APQ-1859-2.02\/24"]}],"id":[{"id":"10.13039\/501100006162","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":["308684\/2023-0"],"award-info":[{"award-number":["308684\/2023-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: The Zika virus (ZIKV) represents an ongoing threat to public health due to its neurological and congenital complications. Even after 10 years since the first major outbreak, correlated with an increase in congenital ZIKV syndrome, there is still no vaccine or treatment for this infection. Among the various existing platforms, DNA vaccines combined with the use of immunoinformatics tools allow for the efficient selection of immunogenic epitopes and immunostimulatory molecules with greater flexibility, in addition to being simple to manufacture and having a higher cost\u2013benefit ratio in production. Methods: In this work, we conducted an integrated approach, combining in silico analyses and in vivo experimental validations, for the development of multi-epitope DNA vaccines against ZIKV. The computational analyses confirmed structural stability, adequate solubility, absence of toxicity, and immune induction potential for constructs based on epitopes from the Envelope (E) and NS1 proteins. Therefore, we evaluated DNA constructs containing the ENV + NS1 epitopes, both with and without fusion to the ssPGIP signal peptide, in BALB\/c mice. Results: Both vaccines increased the population of CD4+ and CD8+ T lymphocytes, in addition to the production of IgG antibodies associated with the Th1 profile. The fusion with ssPGIP broadened the response, stimulating the release of Th1, Th2, and Th17 cytokines, as well as enhancing antibody formation. In contrast, its absence was associated with a slight increase in CD4+ and CD8+ T cells, accompanied by restricted cytokine production. Conclusions: These results indicate that epitope-targeted techniques offer a viable and safe method for inducing robust immune responses, demonstrating that combining immunoinformatics methods with early preclinical testing is an effective strategy for ZIKV vaccine development. Furthermore, although the present study focused on initial immunogenic characterization, future studies involving viral challenge in a suitable animal model will be essential to conclusively determine the protective efficacy of these vaccine candidates.<\/jats:p>","DOI":"10.3390\/vaccines14010031","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and Immunogenicity Assessment of a Multi-Epitope Antigen Against Zika Virus: An In Silico and In Vivo Approach"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4453-8238","authenticated-orcid":false,"given":"L\u00edgia Rosa Sales","family":"Leal","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1573-3000","authenticated-orcid":false,"given":"Matheus Gardini Am\u00e2ncio Marques","family":"de Sena","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-1275","authenticated-orcid":false,"given":"Maria da Concei\u00e7\u00e3o Viana","family":"Inven\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0715-8674","authenticated-orcid":false,"given":"Ingrid Andr\u00eassa","family":"de Moura","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-5712","authenticated-orcid":false,"given":"Andr\u00e9 Luiz Santos de","family":"Jesus","sequence":"additional","affiliation":[{"name":"Federal Institute of Education, Science and Technology of Mato Grosso\u2013Lucas do Rio Verde Advanced Campus, Lucas do Rio Verde 78455-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8780-202X","authenticated-orcid":false,"given":"Georon Ferreira","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological and Antitumor Analysis, Keizo Asami Immunopathology Laboratory, Department of Antibiotics, Bioscience Center, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara Rafaela da Silva","family":"Barros","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological and Antitumor Analysis, Keizo Asami Immunopathology Laboratory, Department of Antibiotics, Bioscience Center, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-0163","authenticated-orcid":false,"given":"Cristiane Moutinho Lagos de","family":"Melo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological and Antitumor Analysis, Keizo Asami Immunopathology Laboratory, Department of Antibiotics, Bioscience Center, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1134-5699","authenticated-orcid":false,"given":"Lindomar Jos\u00e9","family":"Pena","sequence":"additional","affiliation":[{"name":"Department of Virology and Experimental Therapy, Aggeu Magalh\u00e3es Institute, Oswaldo Cruz Foundation, Recife 50740-465, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7384-6248","authenticated-orcid":false,"given":"Francesca","family":"Paolini","sequence":"additional","affiliation":[{"name":"HPV-UNIT-UOSD Tumor Immunology and Immunotherapy, IRCCS Regina Elena National Cancer Institute, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2322-6857","authenticated-orcid":false,"given":"Aldo","family":"Venuti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"},{"name":"HPV-UNIT-UOSD Tumor Immunology and Immunotherapy, IRCCS Regina Elena National Cancer Institute, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8341-7877","authenticated-orcid":false,"given":"Anna J\u00e9ssica Duarte","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4957-9549","authenticated-orcid":false,"given":"Antonio Carlos","family":"de Freitas","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Studies and Experimental Therapy\u2014LEMTE, Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jneuroim.2017.03.001","article-title":"Zika Virus: History, Epidemiology, Transmission, and Clinical Presentation","volume":"308","author":"Song","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virol.2020.01.015","article-title":"Zika Virus-Spread, Epidemiology, Genome, Transmission Cycle, Clinical Manifestation, Associated Challenges, Vaccine and Antiviral Drug Development","volume":"543","author":"Pielnaa","year":"2020","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Capasso, A., Ompad, D.C., Vieira, D.L., Wilder-Smith, A., and Tozan, Y. (2019). Incidence of Guillain-Barr\u00e9 Syndrome (GBS) in Latin America and the Caribbean before and during the 2015\u20132016 Zika Virus Epidemic: A Systematic Review and Meta-Analysis. PLoS Neglected Trop. Dis., 13.","DOI":"10.2139\/ssrn.3320145"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"taaa227","DOI":"10.1093\/jtm\/taaa227","article-title":"Public Health Emergencies of International Concern: A Historic Overview","volume":"27","author":"Osman","year":"2020","journal-title":"J. Travel. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1053\/jinf.2001.0802","article-title":"Dengue and Other Emerging Flaviviruses","volume":"42","author":"Solomon","year":"2001","journal-title":"J. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Santana, L.M.B., de Moura, I.A., Mouzinho Ramos Tanaka, Y., and Fran\u00e7a, R.F.d.O. (2025). Zika Virus: A Review of Biology, Clinical Impacts, and Coinfections. Viruses, 17.","DOI":"10.3390\/v17050637"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.24171\/j.phrp.2022.0101","article-title":"Zika Virus as an Emerging Arbovirus of International Public Health Concern","volume":"13","author":"Vaziri","year":"2022","journal-title":"Osong Public Health Res. Perspect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/S1473-3099(20)30733-7","article-title":"Safety and Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: An Observer-Blind, Randomised, Phase 1 Trial","volume":"21","author":"Han","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1056\/NEJMoa1708120","article-title":"Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine","volume":"385","author":"Tebas","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S1473-3099(23)00192-5","article-title":"Safety and Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Adults Primed with a Japanese Encephalitis Virus or Yellow Fever Virus Vaccine in the USA: A Phase 1, Randomised, Double-Blind, Placebo-Controlled Clinical Trial","volume":"23","author":"Koren","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41541-024-00927-8","article-title":"Ad26.M.Env ZIKV Vaccine Protects Pregnant Rhesus Macaques and Fetuses against Zika Virus Infection","volume":"9","author":"Martinot","year":"2024","journal-title":"npj Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Roozitalab, A., Zhang, J., Zhang, C., Tang, Q., and Zhao, R.Y. (2025). The Evolving Role of Zika Virus Envelope Protein in Viral Entry and Pathogenesis. Viruses, 17.","DOI":"10.3390\/v17060817"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.coviro.2012.02.011","article-title":"Degrees of Maturity: The Complex Structure and Biology of Flaviviruses","volume":"2","author":"Pierson","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eabe4507","DOI":"10.1126\/sciadv.abe4507","article-title":"The Structure of an Infectious Immature Flavivirus Redefines Viral Architecture and Maturation","volume":"7","author":"Newton","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, X., Jia, R., Shen, H., Wang, M., Yin, Z., and Cheng, A. (2017). Structures and Functions of the Envelope Glycoprotein in Flavivirus Infections. Viruses, 9.","DOI":"10.3390\/v9110338"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e00055-16","DOI":"10.1128\/MMBR.00055-16","article-title":"The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis","volume":"81","author":"Heinz","year":"2017","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ngono, A.E., Young, M.P., Bunz, M., Xu, Z., Hattakam, S., Vizcarra, E., Regla-Nava, J.A., Tang, W.W., Yamabhai, M., and Wen, J. (2019). CD4+ T Cells Promote Humoral Immunity and Viral Control during Zika Virus Infection. PLoS Pathog, 15, Correction in PLoS Pathog. 2019, 15, e1007821. https:\/\/doi.org\/10.1371\/journal.ppat.1007821.","DOI":"10.1371\/journal.ppat.1007821"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13567-021-00966-2","article-title":"Structure and Function of Capsid Protein in Flavivirus Infection and Its Applications in the Development of Vaccines and Therapeutics","volume":"52","author":"Zhang","year":"2021","journal-title":"Vet. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S935","DOI":"10.1093\/infdis\/jix515","article-title":"Zika Virus Structure, Maturation, and Receptors","volume":"216","author":"Sirohi","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1080\/21645515.2020.1826798","article-title":"DENV-3 Precursor Membrane (prM) Glycoprotein Enhances E Protein Immunogenicity and Confers Protection against DENV-2 Infections in a Murine Model","volume":"17","author":"Dias","year":"2021","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2218899120","DOI":"10.1073\/pnas.2218899120","article-title":"prM-Reactive Antibodies Reveal a Role for Partially Mature Virions in Dengue Virus Pathogenesis","volume":"120","author":"Dowd","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14769","DOI":"10.1038\/s41598-017-15039-8","article-title":"A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model","volume":"7","author":"Brault","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pattnaik, A., Sahoo, B.R., and Pattnaik, A.K. (2020). Current Status of Zika Virus Vaccines: Successes and Challenges. Vaccines, 8.","DOI":"10.3390\/vaccines8020266"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, S., He, Y., Wu, Z., Wang, M., Jia, R., Zhu, D., Liu, M., Zhao, X., Yang, Q., and Wu, Y. (2023). Secretory Pathways and Multiple Functions of Nonstructural Protein 1 in Flavivirus Infection. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1205002"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1586\/14760584.2016.1124762","article-title":"Molecular Mechanisms for Enhanced DNA Vaccine Immunogenicity","volume":"15","author":"Li","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1080\/21645515.2017.1330236","article-title":"Advancements in DNA Vaccine Vectors, Non-Mechanical Delivery Methods, and Molecular Adjuvants to Increase Immunogenicity","volume":"13","author":"Suschak","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25151355221100218","DOI":"10.1177\/25151355221100218","article-title":"Predicting Epitopes for Vaccine Development Using Bioinformatics Tools","volume":"10","author":"Yurina","year":"2022","journal-title":"Ther. Adv. Vaccines Immunother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"190907","DOI":"10.1098\/rsos.190907","article-title":"Reverse Vaccinology and Subtractive Genomics Reveal New Therapeutic Targets against Mycoplasma Pneumoniae: A Causative Agent of Pneumonia","volume":"6","author":"Jaiswal","year":"2019","journal-title":"R. Soc. Open Sci."},{"key":"ref_29","unstructured":"Sharma, A.K., and Sharma, V. (2024). Chapter 7 Immunoinformatics: Computational Keys to Immune System Secrets. Bioinformatics: Drug Discovery, De Gruyter."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/21645515.2017.1264766","article-title":"A Plant Protein Signal Sequence Improved Humoral Immune Response to HPV Prophylactic and Therapeutic DNA Vaccines","volume":"13","author":"Massa","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1016\/j.vaccine.2021.03.065","article-title":"Pichia Pastoris Displaying ZIKV Protein Epitopes from the Envelope and NS1 Induce in Vitro Immune Activation","volume":"39","author":"Silva","year":"2021","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Silva, A.J.D., de Jesus, A.L.S., Leal, L.R.S., de Mac\u00eado, L.S., da Silva Barros, B.R., de Sousa, G.F., da Paz Le\u00f4ncio Alves, S., Pena, L.J., de Melo, C.M.L., and de Freitas, A.C. (2023). Whole Yeast Vaccine Displaying ZIKV B and T Cell Epitopes Induces Cellular Immune Responses in the Murine Model. Pharmaceutics, 15.","DOI":"10.20944\/preprints202305.1243.v1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00900-17","DOI":"10.1128\/JVI.00900-17","article-title":"CD8+ T Cell Immune Response in Immunocompetent Mice during Zika Virus Infection","volume":"91","author":"Huang","year":"2017","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Badolato-Corr\u00eaa, J., Carvalho, F.R., Paiva, I.A., Familiar-Macedo, D., Dias, H.G., Pauvolid-Corr\u00eaa, A., Fernandes-Santos, C., Lima, M.d.R.Q., Gandini, M., and Silva, A.A. (2021). Differential Longevity of Memory CD4 and CD8 T Cells in a Cohort of the Mothers with a History of ZIKV Infection and Their Children. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.610456"},{"key":"ref_35","first-page":"46","article-title":"Highly Conserved Epitopes of ZIKA Envelope Glycoprotein May Act as a Novel Peptide Vaccine with High Coverage: Immunoinformatics Approach","volume":"4","author":"Badawi","year":"2016","journal-title":"Am. J. Biomed. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.apjtm.2016.07.004","article-title":"Prediction of Promiscuous T-Cell Epitopes in the Zika Virus Polyprotein: An In Silico Approach","volume":"9","author":"Dar","year":"2016","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.meegid.2016.08.037","article-title":"Computational Prediction and Analysis of Potential Antigenic CTL Epitopes in Zika Virus: A First Step towards Vaccine Development","volume":"45","author":"Dikhit","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.addr.2012.09.039","article-title":"Fusion Protein Linkers: Property, Design and Functionality","volume":"65","author":"Chen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e225","DOI":"10.1093\/bioinformatics\/btl318","article-title":"A Tale of Two Tails: Why Are Terminal Residues of Proteins Exposed?","volume":"23","author":"Jacob","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-2567.2010.03268.x","article-title":"MHC Class II Epitope Predictive Algorithms","volume":"130","author":"Nielsen","year":"2010","journal-title":"Immunology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1080\/07391102.2020.1850357","article-title":"Design of a Multi-Epitope-Based Vaccine Targeting M-Protein of SARS-CoV2: An Immunoinformatics Approach","volume":"40","author":"Ayyagari","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for Structure Building and Analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1080\/22221751.2019.1614885","article-title":"Convalescent Patient-Derived Monoclonal Antibodies Targeting Different Epitopes of E Protein Confer Protection against Zika Virus in a Neonatal Mouse Model","volume":"8","author":"Niu","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41591-019-0746-2","article-title":"Potent Zika and Dengue Cross-Neutralizing Antibodies Induced by Zika Vaccination in a Dengue-Experienced Donor","volume":"26","author":"Dussupt","year":"2020","journal-title":"Nat. Med."},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"e01049-17","DOI":"10.1128\/JVI.01049-17","article-title":"Monoclonal Antibodies against Zika Virus: Therapeutics and Their Implications for Vaccine Design","volume":"91","author":"Wang","year":"2017","journal-title":"J. Virol."},{"key":"ref_49","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_50","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_51","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature20564","article-title":"Neutralizing Human Antibodies Prevent Zika Virus Replication and Fetal Disease in Mice","volume":"540","author":"Sapparapu","year":"2016","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1016\/j.celrep.2019.02.062","article-title":"Structural Basis for Neutralization and Protection by a Zika Virus-Specific Human Antibody","volume":"26","author":"Wang","year":"2019","journal-title":"Cell Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"369ra179","DOI":"10.1126\/scitranslmed.aai8336","article-title":"Molecular Determinants of Human Neutralizing Antibodies Isolated from a Patient Infected with Zika Virus","volume":"8","author":"Wang","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.hlife.2024.05.003","article-title":"Structural Insights into the Distinct Protective Mechanisms of Human Antibodies Targeting ZIKV NS1","volume":"2","author":"Pan","year":"2024","journal-title":"hLife"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved Predictions of MHC Antigen Presentation by Concurrent Motif Deconvolution and Integration of MS MHC Eluted Ligand Data","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tuff\u00e9ry, P., and Derreumaux, P. (2023). A Refined pH-Dependent Coarse-Grained Model for Peptide Structure Prediction in Aqueous Solution. Front. Bioinform., 3.","DOI":"10.3389\/fbinf.2023.1113928"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-2269-7_19","article-title":"Small-Molecule Library Screening by Docking with PyRx","volume":"1263","author":"Dallakyan","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_60","unstructured":"(2025, December 02). BIOVIA Discovery Studio Visualizer\u2014Dassault Syst\u00e8mes. Available online: https:\/\/discover.3ds.com\/discovery-studio-visualizer-download."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"044130","DOI":"10.1063\/5.0014475","article-title":"Scalable Molecular Dynamics on CPU and GPU Architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/acs.jctc.5b00935","article-title":"CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM\/OpenMM Simulations Using the CHARMM36 Additive Force Field","volume":"12","author":"Lee","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array Programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"ref_65","unstructured":"McKinney, W. (July, January 28). Data Structures for Statistical Computing in Python. Proceedings of the 9th Python in Science Conference, Austin, TX, USA."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D Graphics Environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.21105\/joss.03021","article-title":"Seaborn: Statistical Data Visualization","volume":"6","author":"Waskom","year":"2021","journal-title":"J. Open Source Softw."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Walker, J.M. (2005). Protein Identification and Analysis Tools on the ExPASy Server. The Proteomics Protocols Handbook, Humana Press.","DOI":"10.1385\/1592598900"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1093\/bioinformatics\/btx345","article-title":"Protein\u2013Sol: A Web Tool for Predicting Protein Solubility from Sequence","volume":"33","author":"Hebditch","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Gupta, S., Kapoor, P., Chaudhary, K., Gautam, A., Kumar, R., Consortium, O.S.D.D., and Raghava, G.P.S. (2013). In Silico Approach for Predicting Toxicity of Peptides and Proteins. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073957"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2\u2014A Server for in Silico Prediction of Allergens","volume":"20","author":"Dimitrov","year":"2014","journal-title":"J. Mol. Model."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.vaccine.2006.09.032","article-title":"Identifying Candidate Subunit Vaccines Using an Alignment-Independent Method Based on Principal Amino Acid Properties","volume":"25","author":"Doytchinova","year":"2007","journal-title":"Vaccine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1745-6150-8-30","article-title":"Designing of Interferon-Gamma Inducing MHC Class-II Binders","volume":"8","author":"Dhanda","year":"2013","journal-title":"Biol. Direct"},{"key":"ref_74","first-page":"263952","article-title":"Prediction of IL4 Inducing Peptides","volume":"2013","author":"Dhanda","year":"2013","journal-title":"J. Immunol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"42851","DOI":"10.1038\/srep42851","article-title":"Computer-Aided Designing of Immunosuppressive Peptides Based on IL-10 Inducing Potential","volume":"7","author":"Nagpal","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.abj8754","article-title":"Accurate Prediction of Protein Structures and Interactions Using a Three-Track Neural Network","volume":"373","author":"Baek","year":"2021","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and Better Reference Data for Improved All-atom Structure Validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"W95","DOI":"10.1093\/nar\/gkaf412","article-title":"CABS-Flex 3.0: An Online Tool for Simulating Protein Structural Flexibility and Peptide Modeling","volume":"53","author":"Zalewski","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Bui, H.-H., Sidney, J., Dinh, K., Southwood, S., Newman, M.J., and Sette, A. (2006). Predicting Population Coverage of T-Cell Epitope-Based Diagnostics and Vaccines. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-153"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e002694","DOI":"10.1136\/jitc-2021-002694","article-title":"Identification and Validation of Viral Antigens Sharing Sequence and Structural Homology with Tumor-Associated Antigens (TAAs)","volume":"9","author":"Ragone","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-0716-0581-3_2","article-title":"Zika Virus Isolation, Purification, and Titration","volume":"2142","author":"Baz","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7971847","DOI":"10.1155\/2016\/7971847","article-title":"Immunogenicity of RSV F DNA Vaccine in BALB\/c Mice","volume":"2016","author":"Eroglu","year":"2016","journal-title":"Adv. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4108","DOI":"10.1016\/j.vaccine.2021.05.098","article-title":"Immunogenic Potential of DNA Vaccine Candidate, ZyCoV-D against SARS-CoV-2 in Animal Models","volume":"39","author":"Dey","year":"2021","journal-title":"Vaccine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"101020","DOI":"10.1016\/j.eclinm.2021.101020","article-title":"Safety and Immunogenicity of a DNA SARS-CoV-2 Vaccine (ZyCoV-D): Results of an Open-Label, Non-Randomized Phase I Part of Phase I\/II Clinical Study by Intradermal Route in Healthy Subjects in India","volume":"38","author":"Momin","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhang, S., He, Z., Wang, H., and Zhai, J. (2025). Signal Peptides: From Molecular Mechanisms to Applications in Protein and Vaccine Engineering. Biomolecules, 15.","DOI":"10.3390\/biom15060897"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s12934-016-0604-6","article-title":"Use of a Sec Signal Peptide Library from Bacillus subtilis for the Optimization of Cutinase Secretion in Corynebacterium glutamicum","volume":"15","author":"Hemmerich","year":"2016","journal-title":"Microb. Cell Factories"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/bit.24776","article-title":"Optimized Signal Peptides for the Development of High Expressing CHO Cell Lines","volume":"110","author":"Kober","year":"2013","journal-title":"Biotechnol. Bioeng."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s10616-017-0109-0","article-title":"Modifications of a Signal Sequence for Antibody Secretion from Insect Cells","volume":"70","author":"Yamaji","year":"2018","journal-title":"Cytotechnology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1177\/205873920601900119","article-title":"Exploiting the Plant Secretory Pathway to Improve the Anticancer Activity of a Plant-Derived HPV16 E7 Vaccine","volume":"19","author":"Franconi","year":"2006","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/14760584.2017.1306441","article-title":"Influence of Protein Fold Stability on Immunogenicity and Its Implications for Vaccine Design","volume":"16","author":"Scheiblhofer","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Sootichote, R., Puangmanee, W., Benjathummarak, S., Kowaboot, S., Yamanaka, A., Boonnak, K., Ampawong, S., Chatchen, S., Ramasoota, P., and Pitaksajjakul, P. (2023). Potential Protective Effect of Dengue NS1 Human Monoclonal Antibodies against Dengue and Zika Virus Infections. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010227"},{"key":"ref_92","doi-asserted-by":"crossref","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":"ref_93","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/labinvest.2008.70","article-title":"Liver Injury Caused by Antibodies against Dengue Virus Nonstructural Protein 1 in a Murine Model","volume":"88","author":"Lin","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_94","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_95","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/infdis\/jiy482","article-title":"Dengue Virus and Zika Virus Serological Cross-Reactivity and Their Impact on Pathogenesis in Mice","volume":"219","author":"Watanabe","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Prasasty, V.D., Grazzolie, K., Rosmalena, R., Yazid, F., Ivan, F.X., and Sinaga, E. (2019). Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches. Microorganisms, 7.","DOI":"10.3390\/microorganisms7080226"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"107459","DOI":"10.1016\/j.compbiolchem.2021.107459","article-title":"Evaluation of Potential MHC-I Allele-Specific Epitopes in Zika Virus Proteins and the Effects of Mutations on Peptide-MHC-I Interaction Studied Using In Silico Approaches","volume":"92","author":"Fernandes","year":"2021","journal-title":"Comput. Biol. Chem."},{"key":"ref_98","unstructured":"Fornusek, L., and Vetvicka, V. (1992). Molecular Biology of Antigen Presentation. Immune System Accessory Cells, CRC Press."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2174\/156652311798192815","article-title":"Novel Strategies to Improve DNA Vaccine Immunogenicity","volume":"11","author":"Coban","year":"2011","journal-title":"Curr. Gene Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jviromet.2008.08.011","article-title":"Immunization with Plasmid DNA Encoding Influenza A Virus Nucleoprotein Fused to a Tissue Plasminogen Activator Signal Sequence Elicits Strong Immune Responses and Protection against H5N1 Challenge in Mice","volume":"154","author":"Luo","year":"2008","journal-title":"J. Virol. Methods"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Hobernik, D., and Bros, M. (2018). DNA Vaccines\u2014How Far from Clinical Use?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113605"},{"key":"ref_102","first-page":"1","article-title":"Improving Mammalian Cell Factories: The Selection of Signal Peptide Has a Major Impact on Recombinant Protein Synthesis and Secretion in Mammalian Cells","volume":"2","author":"Stern","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00430-015-0445-7","article-title":"Cytokine Kinetics of Zika Virus-Infected Patients from Acute to Reconvalescent Phase","volume":"205","author":"Tappe","year":"2016","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1093\/infdis\/jix261","article-title":"Specific Biomarkers Associated with Neurological Complications and Congenital Central Nervous System Abnormalities from Zika Virus-Infected Patients in Brazil","volume":"216","author":"Kam","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Barros, J.B.d.S., da Silva, P.A.N., Koga, R.d.C.R., Gonzalez-Dias, P., Carmo Filho, J.R., Nagib, P.R.A., Coelho, V., Nakaya, H.I., Fonseca, S.G., and Pfrimer, I.A.H. (2018). Acute Zika Virus Infection in an Endemic Area Shows Modest Proinflammatory Systemic Immunoactivation and Cytokine-Symptom Associations. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00821"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Pardy, R.D., Rajah, M.M., Condotta, S.A., Taylor, N.G., Sagan, S.M., and Richer, M.J. (2017). Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8+ T Cell Epitope in Immunocompetent Mice. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006184"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Nazerai, L., Sch\u00f8ller, A.S., Bassi, M.R., Buus, S., Stryhn, A., Christensen, J.P., and Thomsen, A.R. (2020). Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01977"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"107566","DOI":"10.1016\/j.celrep.2020.107566","article-title":"CD4+ T Cells Cross-Reactive with Dengue and Zika Viruses Protect against Zika Virus Infection","volume":"31","author":"Wen","year":"2020","journal-title":"Cell Rep."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Apostolico, J.d.S., Lunardelli, V.A.S., Boscardin, S.B., Botosso, V.F., Astray, R.M., Kalil, J., de Almeida, R.P., Cunha-Neto, E., and Rosa, D.S. (2024). Durable Cellular Immune Response against Inactivated ZIKV and Envelope Proteins in ZIKV-Infected Women during Pregnancy. Front. Trop. Dis., 5.","DOI":"10.3389\/fitd.2024.1369608"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wijeratne, D.T., Fernando, S., Gomes, L., Jeewandara, C., Ginneliya, A., Samarasekara, S., Wijewickrama, A., Hardman, C.S., Ogg, G.S., and Malavige, G.N. (2018). Quantification of Dengue Virus Specific T Cell Responses and Correlation with Viral Load and Clinical Disease Severity in Acute Dengue Infection. PLoS Neglected Trop. Dis., 12.","DOI":"10.1101\/325944"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.coviro.2020.07.018","article-title":"Protection against Dengue Virus Requires a Sustained Balance of Antibody and T Cell Responses","volume":"43","author":"Valentine","year":"2020","journal-title":"Curr. Opin. Virol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/imm.12681","article-title":"CD4+ and CD8+ T-Cell Immunity to Dengue\u2014Lessons for the Study of Zika Virus","volume":"150","author":"Rivino","year":"2017","journal-title":"Immunology"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Mapalagamage, M., Weiskopf, D., Sette, A., and De Silva, A.D. (2022). Current Understanding of the Role of T Cells in Chikungunya, Dengue and Zika Infections. Viruses, 14.","DOI":"10.3390\/v14020242"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1084\/jem.20121517","article-title":"Revealing the Role of CD4(+) T Cells in Viral Immunity","volume":"209","author":"Sant","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1038\/s41467-019-13438-1","article-title":"CD4+ T Cell Help Creates Memory CD8+ T Cells with Innate and Help-Independent Recall Capacities","volume":"10","author":"Ahrends","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1038\/s41467-019-11754-0","article-title":"ZIKV Infection Induces Robust Th1-like Tfh Cell and Long-Term Protective Antibody Responses in Immunocompetent Mice","volume":"10","author":"Liang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Hassert, M., Wolf, K.J., Schwetye, K.E., DiPaolo, R.J., Brien, J.D., and Pinto, A.K. (2018). CD4+T Cells Mediate Protection against Zika Associated Severe Disease in a Mouse Model of Infection. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007237"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41564-019-0618-z","article-title":"Evolution of the Innate and Adaptive Immune Response in Women with Acute Zika Virus Infection","volume":"5","author":"Tonnerre","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.1016\/j.vaccine.2021.07.036","article-title":"Development of a Novel ZIKV Vaccine Comprised of Immunodominant CD4+ and CD8+ T Cell Epitopes Identified through Comprehensive Epitope Mapping in Zika Virus Infected Mice","volume":"39","author":"Sun","year":"2021","journal-title":"Vaccine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3201\/eid2502.181286","article-title":"Zika Virus IgM Detection and Neutralizing Antibody Profiles 12\u201319 Months after Illness Onset","volume":"25","author":"Griffin","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e0040021","DOI":"10.1128\/JCM.00400-21","article-title":"The Specificity of the Persistent IgM Neutralizing Antibody Response in Zika Virus Infections among Individuals with Prior Dengue Virus Exposure","volume":"59","author":"Calvert","year":"2021","journal-title":"J. Clin. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e2504005","DOI":"10.71150\/jm.2504005","article-title":"Mouse Strain-Dependent Neutralizing Antibody Responses to Zika Virus Vaccines","volume":"63","author":"Seo","year":"2025","journal-title":"J. Microbiol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/1\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:47:26Z","timestamp":1766987246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/1\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":122,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["vaccines14010031"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14010031","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]}}}