{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:50:00Z","timestamp":1789905000706,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T00:00:00Z","timestamp":1516233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 AI116813"],"award-info":[{"award-number":["R01 AI116813"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21 NS100477"],"award-info":[{"award-number":["R21 NS100477"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21AI127988"],"award-info":[{"award-number":["R21AI127988"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain\u2013Barr\u00e9 syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes. Many of these approaches have leveraged lessons learned from past experience with Dengue and other flavivirus vaccines.<\/jats:p>","DOI":"10.3390\/vaccines6010007","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T12:19:48Z","timestamp":1516277988000},"page":"7","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Development of Zika Virus Vaccines"],"prefix":"10.3390","volume":"6","author":[{"given":"Huda","family":"Makhluf","sequence":"first","affiliation":[{"name":"Department of Mathematics and Natural Sciences, National University, La Jolla, CA 92037, USA"},{"name":"Center for Infectious Disease, La Jolla Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujan","family":"Shresta","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease, La Jolla Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus. I. Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/S0140-6736(16)00562-6","article-title":"Guillain-Barr\u00e9 Syndrome outbreak caused by ZIKA virus infection in French Polynesia","volume":"387","author":"Blake","year":"2016","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e3257","DOI":"10.1097\/MD.0000000000003257","article-title":"Guillain\u2013Barr\u00e9 Syndrome (42 Cases) Occurring During a Zika Virus Outbreak in French Polynesia","volume":"95","author":"Watrin","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3201\/eid1408.080287","article-title":"Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007","volume":"14","author":"Lanciotti","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1056\/NEJMp1600297","article-title":"Zika Virus in the Americas\u2014Yet Another Arbovirus Threat","volume":"374","author":"Fauci","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pmed.1002203","article-title":"Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain\u2013Barr\u00e9 Syndrome: Systematic Review","volume":"14","author":"Krauer","year":"2017","journal-title":"PLoS Med."},{"key":"ref_7","unstructured":"PAHO (2017). PAHO Reports: Pan American Health Organization\/World Health Organization. Zika Suspected and Confirmed Cases Reported by Countries and Territories in the Americas Cumulative Cases, 2015\u20132017, PAHO."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2807\/1560-7917.ES.2016.21.32.30314","article-title":"Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016","volume":"21","author":"Nicastri","year":"2016","journal-title":"Eurosurveillance"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3201\/eid2102.141363","article-title":"Potenial sexual transmission of Zika virus","volume":"21","author":"Musso","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"880","DOI":"10.3201\/eid1705.101939","article-title":"Probable Non-Vector-borne Transmission of Zika Virus, Colorado, USA","volume":"17","author":"Foy","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"242","DOI":"10.15585\/mmwr.mm6509e2","article-title":"Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy\u2014Brazil, 2015","volume":"65","author":"Henriques","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.celrep.2016.07.049","article-title":"Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype","volume":"16","author":"Dowd","year":"2016","journal-title":"Cell Rep."},{"key":"ref_13","unstructured":"(2017, November 22). World Health Organization (WHO). Available online: http:\/\/www.who.int\/immunization\/research\/vaccine_pipeline_tracker_spreadsheet\/en\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature18952","article-title":"Vaccine protection against Zika virus from Brazil","volume":"536","author":"Larocca","year":"2016","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1126\/science.aai9137","article-title":"Rapid development of a DNA vaccine for Zika virus","volume":"354","author":"Dowd","year":"2016","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1093\/infdis\/jir054","article-title":"A west nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial","volume":"203","author":"Ledgerwood","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_17","first-page":"1","article-title":"Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: Randomised, open-label, phase 1 clinical trials","volume":"6736","author":"Gaudinski","year":"2017","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Muthumani, K., Griffin, B.D., Agarwal, S., Kudchodkar, S.B., Reuschel, E.L., Choi, H., Kraynyak, K.A., Duperret, E.K., Keaton, A.A., and Chung, C. (2016). In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and aactive immunisation with a prMEnv DNA vaccine. NPJ Vaccines, 1.","DOI":"10.1038\/npjvaccines.2016.21"},{"key":"ref_19","unstructured":"Tebas, P., Roberts, C.C., Muthumani, K., Reuschel, E.L., Kudchodkar, S.B., Zaidi, F.I., White, S., Khan, A.S., Racine, T., and Choi, H. (2017). Safety and Immunogenicity of an Anti\u2013Zika Virus DNA Vaccine\u2014Preliminary Report. N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1128\/JVI.02950-14","article-title":"Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors","volume":"89","author":"Abbink","year":"2015","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1126\/science.aah6157","article-title":"Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys","volume":"353","author":"Abbink","year":"2016","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ebiom.2016.09.028","article-title":"Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation","volume":"13","author":"Kim","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature21428","article-title":"Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination","volume":"543","author":"Pardi","year":"2017","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.cell.2017.02.017","article-title":"Erratum: Modified mRNA Vaccines Protect against Zika Virus Infection","volume":"168","author":"Richner","year":"2017","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/S0140-6736(14)61060-6","article-title":"Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: A phase 3, randomised, observer-masked, placebo-controlled trial","volume":"384","author":"Capeding","year":"2014","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e378","DOI":"10.1016\/S1473-3099(17)30362-6","article-title":"Achieving safe, effective, and durable Zika virus vaccines: Lessons from dengue","volume":"17","author":"Halstead","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.tim.2016.06.002","article-title":"Neuroteratogenic Viruses and Lessons for Zika Virus Models","volume":"24","author":"Kim","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nm.4322","article-title":"A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models","volume":"23","author":"Shan","year":"2017","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xie, X., Yang, Y., Muruato, A.E., Zou, J., Shan, C., Nunes, B.T.D., Medeiros, D.B., Vasconcelos, P.F., Weaver, S.C., and Rossi, S.L. (2017). Understanding Zika Virus Stability and Developing a Chimeric Vaccine through Functional Analysis. MBio Am. Soc. Microbiol., 8.","DOI":"10.1128\/mBio.02134-16"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.immuni.2017.02.005","article-title":"Prospects for a Zika Virus Vaccine","volume":"46","author":"Barouch","year":"2017","journal-title":"Immunity"},{"key":"ref_31","first-page":"1","article-title":"Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: Phase 1, randomised, double-blind, placebo-controlled clinical trials","volume":"6736","author":"Modjarrad","year":"2017","journal-title":"Lancet"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.chom.2016.12.010","article-title":"Mapping and Role of the CD8+ T Cell Response During Primary Zika Virus Infection in Mice","volume":"21","author":"Vizcarra","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wen, J., Elong Ngono, A., Angel Regla-Nava, J., Kim, K., Gorman, M.J., Diamond, M.S., and Shresta, S. (2017). Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge. Nat. Commun., 8.","DOI":"10.1038\/s41467-017-01669-z"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wen, J., Tang, W.W., Sheets, N., Ellison, J., Sette, A., Kim, K., and Shresta, S. (2017). Identification of Zika virus epitopes reveals immunodominant and protective roles for dengue virus cross-reactive CD8+ T cells. Nat. Microbiol., 2.","DOI":"10.1038\/nmicrobiol.2017.36"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","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_37","doi-asserted-by":"crossref","unstructured":"De Alwis, R., Williams, K.L., Schmid, M.A., Lai, C.Y., Patel, B., Smith, S.A., Crowe, J.E., Wang, W.K., Harris, E., and De Silva, A.M. (2014). Dengue Viruses Are Enhanced by Distinct Populations of Serotype Cross-Reactive Antibodies in Human Immune Sera. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004386"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1126\/science.aal4365","article-title":"Enhancement of Zika virus athogenesis by preexisting antiflavivirus immunity","volume":"356","author":"Bardina","year":"2017","journal-title":"Science"},{"key":"ref_39","first-page":"1","article-title":"Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","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."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/6\/1\/7\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:51:43Z","timestamp":1760194303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/6\/1\/7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,18]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["vaccines6010007"],"URL":"https:\/\/doi.org\/10.3390\/vaccines6010007","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,18]]}}}