{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:31:13Z","timestamp":1789079473910,"version":"build-2803163510"},"reference-count":131,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>West Nile Virus (WNV) belongs to the orthoflavivirus genus and is part of the Flaviviridae family, which includes the Japanese encephalitis virus, Dengue virus, Zika virus, and yellow fever virus. WNV circulates among birds and mosquitoes, posing infection risks to humans and mammals. The significant rise in WNV\u2019s geographic spread and infection rates over the past five decades has prompted urgent public health concerns, driving the need for accelerated vaccine research. The development of a vaccine for WNV infection presents several challenges, primarily due to the virus\u2019s complex biology, the risk of cross-reactivity with other flaviviruses, safety concerns such as antibody-dependent enhancement (ADE), and the economic and logistical hurdles in vaccine production. Despite significant research efforts, no human vaccine has been approved, although several candidates are in various stages of development. The current review offers a comprehensive summary of the latest progress and the concomitant challenges in the development of vaccines. It also discusses the role of host\u2013pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis in facilitating the advancement of vaccines.<\/jats:p>","DOI":"10.3390\/vaccines14060499","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Advances and Challenges in Vaccine Development for West Nile Virus (WNV) Infection"],"prefix":"10.3390","volume":"14","author":[{"given":"Anjali","family":"Gupta","sequence":"first","affiliation":[{"name":"New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarti","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Galveston National Laboratory, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirtika","family":"Jha","sequence":"additional","affiliation":[{"name":"Tata Institute for Genetics and Society, Bengaluru 560065, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogita","family":"Rawat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard University, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urvashi","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard University, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Khasa","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailendra","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Galveston National Laboratory, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1126\/science.286.5448.2333","article-title":"Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States","volume":"286","author":"Lanciotti","year":"1999","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1586\/14760584.2014.906309","article-title":"Current trends in West Nile virus vaccine development","volume":"13","author":"Amanna","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1080\/21645515.2019.1621149","article-title":"West Nile virus vaccines\u2014Current situation and future directions","volume":"15","author":"Ulbert","year":"2019","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Flores, H.E., Pinzon Burgos, E.F., Camacho Ortega, S., Heredia, A., and Chua, J.V. (2025). From Antibodies to Immunity: Assessing Correlates of Flavivirus Protection and Cross-Reactivity. Vaccines, 13.","DOI":"10.3390\/vaccines13050449"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1128\/JVI.02042-09","article-title":"Interplay of RNA elements in the dengue virus 5\u2032 and 3\u2032 ends required for viral RNA replication","volume":"84","author":"Friebe","year":"2010","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.1128\/JVI.75.14.6719-6728.2001","article-title":"Essential role of cyclization sequences in flavivirus RNA replication","volume":"75","author":"Khromykh","year":"2001","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1021\/bi952398v","article-title":"Evidence for the existence of a pseudoknot structure at the 3\u2032 terminus of the flavivirus genomic RNA","volume":"35","author":"Shi","year":"1996","journal-title":"Biochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1146\/annurev.micro.56.012302.160654","article-title":"The molecular biology of West Nile Virus: A new invader of the western hemisphere","volume":"56","author":"Brinton","year":"2002","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_9","first-page":"323","article-title":"Replication and gene function in Kunjin virus","volume":"267","author":"Westaway","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1099\/0022-1317-72-4-851","article-title":"In vitro synthesis of West Nile virus proteins indicates that the amino-terminal segment of the NS3 protein contains the active centre of the protease which cleaves the viral polyprotein after multiple basic amino acids","volume":"72","author":"Wengler","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/viro.1993.1587","article-title":"The NS 3 nonstructural protein of flaviviruses contains an RNA triphosphatase activity","volume":"197","author":"Wengler","year":"1993","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0065-3527(03)59002-9","article-title":"Molecular biology of flaviviruses","volume":"59","author":"Lindenbach","year":"2003","journal-title":"Adv. Virus Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.virusres.2008.05.015","article-title":"Interferon antagonist function of Japanese encephalitis virus NS4A and its interaction with DEAD-box RNA helicase DDX42","volume":"137","author":"Lin","year":"2008","journal-title":"Virus Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12225","DOI":"10.1128\/JVI.78.22.12225-12235.2004","article-title":"Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role for the flavivirus nonstructural protein NS2A in inhibition of beta interferon promoter-driven transcription","volume":"78","author":"Liu","year":"2004","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1128\/JVI.80.5.2396-2404.2006","article-title":"A single amino acid substitution in the West Nile virus nonstructural protein NS2A disables its ability to inhibit alpha\/beta interferon induction and attenuates virus virulence in mice","volume":"80","author":"Liu","year":"2006","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8004","DOI":"10.1128\/JVI.79.13.8004-8013.2005","article-title":"Inhibition of alpha\/beta interferon signaling by the NS4B protein of flaviviruses","volume":"79","author":"Ashour","year":"2005","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3390\/v3020160","article-title":"Flavivirus cell entry and membrane fusion","volume":"3","author":"Smit","year":"2011","journal-title":"Viruses"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1128\/JVI.80.3.1290-1301.2006","article-title":"West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection","volume":"80","author":"Davis","year":"2006","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"54533","DOI":"10.1074\/jbc.M410208200","article-title":"Interaction of West Nile virus with alpha v beta 3 integrin mediates virus entry into cells","volume":"279","author":"Chu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5212","DOI":"10.1128\/JVI.00008-08","article-title":"West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of alphavbeta3 integrin","volume":"82","author":"Medigeshi","year":"2008","journal-title":"J. Virol."},{"key":"ref_21","first-page":"565","article-title":"Phosphatidylserine receptors: Enhancers of enveloped virus entry and infection","volume":"468\u2013470","author":"Maury","year":"2014","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.chom.2012.08.009","article-title":"The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry","volume":"12","author":"Meertens","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.celrep.2016.06.028","article-title":"Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics","volume":"16","author":"Savidis","year":"2016","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1128\/JVI.02210-06","article-title":"Rab 5 is required for the cellular entry of dengue and West Nile viruses","volume":"81","author":"Krishnan","year":"2007","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12647","DOI":"10.1128\/JVI.78.22.12647-12656.2004","article-title":"Serotype-specific entry of dengue virus into liver cells: Identification;of the 37-kilodalton\/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor","volume":"78","author":"Thepparit","year":"2004","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jmr.866","article-title":"Immunochemical and single molecule force spectroscopy studies of specific interaction between the laminin binding protein and the West Nile virus surface glycoprotein E domain II","volume":"21","author":"Bogachek","year":"2008","journal-title":"J. Mol. Recognit."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10543","DOI":"10.1128\/JVI.78.19.10543-10555.2004","article-title":"Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway","volume":"78","author":"Chu","year":"2004","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Duan, Y., Zeng, M., Jiang, B., Zhang, W., Wang, M., Jia, R., Zhu, D., Liu, M., Zhao, X., and Yang, Q. (2019). Flavivirus RNA-Dependent RNA Polymerase Interacts with Genome UTRs and Viral Proteins to Facilitate Flavivirus RNA Replication. Viruses, 11.","DOI":"10.3390\/v11100929"},{"key":"ref_29","first-page":"353","article-title":"Interaction of West Nile and Kunjin viruses with cellular components during morphogenesis","volume":"267","author":"Ng","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"427814","DOI":"10.1155\/2015\/427814","article-title":"Interaction between Flavivirus and Cytoskeleton during Virus Replication","volume":"2015","author":"Foo","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s12250-019-00086-4","article-title":"The Role of Host Cytoskeleton in Flavivirus Infection","volume":"34","author":"Zhang","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"268","DOI":"10.4269\/ajtmh.2009.80.268","article-title":"Host selection by Culex pipiens mosquitoes and West Nile virus amplification","volume":"80","author":"Hamer","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"662","DOI":"10.2987\/8756-971X(2006)22[662:VCOCIA]2.0.CO;2","article-title":"Vector competence of Culiseta incidens and Culex thriambus for West Nile virus","volume":"22","author":"Reisen","year":"2006","journal-title":"J. Am. Mosq. Control Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/jmedent\/45.3.483","article-title":"Arbovirus transmission by Culex nigripalpus in Florida, 2005","volume":"45","author":"Vitek","year":"2008","journal-title":"J. Med. Entomol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/jmedent\/45.1.125","article-title":"Culex pipiens (Diptera: Culicidae): A bridge vector of West Nile virus to humans","volume":"45","author":"Hamer","year":"2008","journal-title":"J. Med. Entomol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/infdis\/93.3.207","article-title":"Isolation of West Nile virus in Israel","volume":"93","author":"Bernkopf","year":"1953","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3181\/00379727-77-18884","article-title":"Isolation from human sera in Egypt of a virus apparently identical to West Nile virus","volume":"77","author":"Melnick","year":"1951","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"719","DOI":"10.3181\/00379727-84-20764","article-title":"Isolation of West Nile virus from hooded crow and rock pigeon in the Nile delta","volume":"84","author":"Work","year":"1953","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_39","first-page":"275","article-title":"Clinical and laboratory observations in an outbreak of West Nile fever in Israel in 1957","volume":"54","author":"Spigland","year":"1958","journal-title":"Harefuah"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1863-2378.2008.01207.x","article-title":"West Nile Virus in the New World: Trends in the spread and proliferation of West Nile Virus in the Western Hemisphere","volume":"56","author":"Artsob","year":"2009","journal-title":"Zoonoses Public Health"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lohitharajah, J., Malavige, G.N., Chua, A.J.S., Ng, M.L., Arambepola, C., and Chang, T. (2015). Emergence of human West Nile Virus infection in Sri Lanka. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1040-7"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"85","DOI":"10.4103\/0972-2327.128561","article-title":"Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity","volume":"17","author":"Maramattom","year":"2014","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/jmv.25325","article-title":"Emergence of human West Nile Virus infection among pediatric population in Madhya Pradesh, India","volume":"91","author":"Tandel","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S1473-3099(04)01128-4","article-title":"West Nile virus: Where are we now?","volume":"4","author":"Granwehr","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/j.1399-3062.2010.00595.x","article-title":"West Nile virus encephalitis acquired via liver transplantation and clinical response to intravenous immunoglobulin: Case report and review of the literature","volume":"13","author":"Rhee","year":"2011","journal-title":"Transpl. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"360","DOI":"10.7326\/0003-4819-141-5-200409070-00010","article-title":"Clinical characteristics and functional outcomes of West Nile Fever","volume":"141","author":"Watson","year":"2004","journal-title":"Ann. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"606","DOI":"10.3390\/v6020606","article-title":"Clinical manifestations and outcomes of West Nile virus infection","volume":"6","author":"Sejvar","year":"2014","journal-title":"Viruses"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1056\/NEJM200106143442401","article-title":"The outbreak of West Nile virus infection in the New York City area in 1999","volume":"344","author":"Nash","year":"2001","journal-title":"N Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1086\/313737","article-title":"The West Nile Virus outbreak of 1999 in New York: The Flushing Hospital experience","volume":"30","author":"Asnis","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"654","DOI":"10.3201\/eid0704.017409","article-title":"West Nile Virus Outbreak Response Working, Clinical findings of West Nile virus infection in hospitalized patients, New York and New Jersey, 2000","volume":"7","author":"Weiss","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1086\/518281","article-title":"The long-term outcomes of human West Nile virus infection","volume":"44","author":"Sejvar","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1128\/JCM.38.11.4066-4071.2000","article-title":"Rapid detection of west nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay","volume":"38","author":"Lanciotti","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_53","first-page":"95986","article-title":"Diagnosis of West Nile virus infections: Evaluation of different laboratory methods","volume":"13","author":"Bogdanic","year":"2024","journal-title":"World J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1111\/ajt.16595","article-title":"Surveillance for West Nile virus disease\u2014United States, 2009\u20132018","volume":"21","author":"McDonald","year":"2021","journal-title":"Am. J. Transpl."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1001\/jama.2013.8042","article-title":"West Nile virus: Review of the literature","volume":"310","author":"Petersen","year":"2013","journal-title":"JAMA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2217\/imt.10.93","article-title":"Vaccines and immunotherapeutics for the prevention and treatment of infections with West Nile virus","volume":"3","author":"Beasley","year":"2011","journal-title":"Immunotherapy"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7334","DOI":"10.1128\/JVI.06867-11","article-title":"Isoflavone agonists of IRF-3 dependent signaling have antiviral activity against RNA viruses","volume":"86","author":"Bedard","year":"2012","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.apjtm.2016.01.033","article-title":"Pharmacodynamics of aminoglycosides and tetracycline derivatives against Japanese encephalitis virus","volume":"9","author":"Topno","year":"2016","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/j.celrep.2018.03.001","article-title":"Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections","volume":"22","author":"Thackray","year":"2018","journal-title":"Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1128\/CVI.00249-07","article-title":"Comparative efficacies of three commercially available vaccines against West Nile Virus (WNV) in a short-duration challenge trial involving an equine WNV encephalitis model","volume":"14","author":"Seino","year":"2007","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1016\/j.vaccine.2018.12.026","article-title":"An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults","volume":"37","author":"Woods","year":"2019","journal-title":"Vaccine"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1016\/j.vaccine.2018.12.020","article-title":"Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine","volume":"37","author":"Quintel","year":"2019","journal-title":"Vaccine"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kaiser, J.A., and Barrett, A.D.T. (2019). Twenty Years of Progress Toward West Nile Virus Vaccine Development. Viruses, 11.","DOI":"10.3390\/v11090823"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Barningham, L., Carr, I.M., Jossi, S., Cole, M., Ponce, A., Short, M., Meneses, C., Lacsina, J.R., Valenzuela, J.G., and Oliveira, F. (2025). AGS-v PLUS, a Mosquito Salivary Peptide Vaccine, Modulates the Response to Aedes Mosquito Bites in Humans. Vaccines, 13.","DOI":"10.3390\/vaccines13101026"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1089\/vim.2000.13.469","article-title":"West Nile virus in the United States: Guidelines for detection, prevention, and control","volume":"13","author":"Gubler","year":"2000","journal-title":"Viral Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1473-3099(02)00368-7","article-title":"West Nile virus","volume":"2","author":"Campbell","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1016\/j.vaccine.2006.11.056","article-title":"Prospective immunization of the endangered California condors (Gymnogyps californianus) protects this species from lethal West Nile virus infection","volume":"25","author":"Chang","year":"2007","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3201\/eid0903.020628","article-title":"Experimental infection of North American birds with the New York 1999 strain of West Nile virus","volume":"9","author":"Komar","year":"2003","journal-title":"Emerg. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1638\/2008-0017.1","article-title":"Pathogenicity of West Nile virus and response to vaccination in sandhill cranes (Grus canadensis) using a killed vaccine","volume":"40","author":"Olsen","year":"2009","journal-title":"J. Zoo Wildl. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1016\/j.vaccine.2005.03.052","article-title":"An inactivated West Nile virus vaccine for domestic geese-efficacy study and a summary of 4 years of field application","volume":"23","author":"Samina","year":"2005","journal-title":"Vaccine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13567-015-0220-1","article-title":"DNA vaccines encoding the envelope protein of West Nile virus lineages 1 or 2 administered intramuscularly, via electroporation and with recombinant virus protein induce partial protection in large falcons (Falco spp.)","volume":"46","author":"Fischer","year":"2015","journal-title":"Vet. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1638\/2008-0029.1","article-title":"West Nile virus seroconversion in penguins after vaccination with a killed virus vaccine or a DNA vaccine","volume":"39","author":"Davis","year":"2008","journal-title":"J. Zoo Wildl. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.3389\/fmicb.2019.01133","article-title":"A Recombinant Subviral Particle-Based Vaccine Protects Magpie (Pica pica) Against West Nile Virus Infection","volume":"10","author":"Camacho","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"78","DOI":"10.4269\/ajtmh.2003.69.78","article-title":"Host-range restriction of chimeric yellow fever-West Nile vaccine in fish crows (Corvus ossifragus)","volume":"69","author":"Langevin","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1089\/vbz.2010.0173","article-title":"Efficacy of three vaccines in protecting Western Scrub-Jays (Aphelocoma californica) from experimental infection with West Nile virus: Implications for vaccination of Island Scrub-Jays (Aphelocoma insularis)","volume":"11","author":"Wheeler","year":"2011","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1637\/0005-2086(2007)51[573:DVOTAC]2.0.CO;2","article-title":"DNA vaccination of the American crow (Corvus brachyrhynchos) provides partial protection against lethal challenge with West Nile virus","volume":"51","author":"Bunning","year":"2007","journal-title":"Avian Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1089\/vbz.2009.0029","article-title":"DNA vaccination of American robins (Turdus migratorius) against West Nile virus","volume":"10","author":"Kilpatrick","year":"2010","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.1016\/j.vaccine.2008.08.011","article-title":"Protective efficacy of a recombinant subunit West Nile virus vaccine in domestic geese (Anser anser)","volume":"26","author":"Jarvi","year":"2008","journal-title":"Vaccine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.vaccine.2012.12.044","article-title":"Domestic goose as a model for West Nile virus vaccine efficacy","volume":"31","author":"Sa","year":"2013","journal-title":"Vaccine"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Schwarz, E.R., and Long, M.T. (2023). Comparison of West Nile Virus Disease in Humans and Horses: Exploiting Similarities for Enhancing Syndromic Surveillance. Viruses, 15.","DOI":"10.3390\/v15061230"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ruiz-Lopez, M.J., Aguilera-Sepulveda, P., Cebrian-Camison, S., Figuerola, J., Magallanes, S., Varona, S., Cuesta, I., Cano-Gomez, C., Sanchez-Mora, P., and Camacho, J. (2023). Re-Emergence of a West Nile Virus (WNV) Variant in South Spain with Rapid Spread Capacity. Viruses, 15.","DOI":"10.3390\/v15122372"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Naveed, A., Eertink, L.G., Wang, D., and Li, F. (2024). Lessons Learned from West Nile Virus Infection: Vaccinations in Equines and Their Implications for One Health Approaches. Viruses, 16.","DOI":"10.3390\/v16050781"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1326154","DOI":"10.3389\/fpubh.2023.1326154","article-title":"Two centuries of vaccination: Historical and conceptual approach and future perspectives","volume":"11","author":"Montero","year":"2023","journal-title":"Front. Public Health"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1084\/jem.137.5.1142","article-title":"Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution","volume":"137","author":"Steinman","year":"1973","journal-title":"J. Exp. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.immuni.2018.08.012","article-title":"B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4(+) T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen","volume":"49","author":"Hong","year":"2018","journal-title":"Immunity"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.smim.2005.05.005","article-title":"Humoral immune response and B-cell functions including immunoglobulin class switch are downregulated in aged mice and humans","volume":"17","author":"Frasca","year":"2005","journal-title":"Semin. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41586-021-03738-2","article-title":"SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses","volume":"596","author":"Turner","year":"2021","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.vetimm.2008.02.002","article-title":"A West Nile virus (WNV) recombinant canarypox virus vaccine elicits WNV-specific neutralizing antibodies and cell-mediated immune responses in the horse","volume":"123","author":"Minke","year":"2008","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_89","first-page":"221","article-title":"Equine vaccine for West Nile virus","volume":"114","author":"Ng","year":"2003","journal-title":"Dev. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1128\/JVI.75.9.4040-4047.2001","article-title":"West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays","volume":"75","author":"Davis","year":"2001","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.3390\/v5102384","article-title":"Vaccines in development against West Nile virus","volume":"5","author":"Brandler","year":"2013","journal-title":"Viruses"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.1016\/j.vaccine.2005.02.020","article-title":"Recombinant canarypox vectored West Nile virus (WNV) vaccine protects dogs and cats against a mosquito WNV challenge","volume":"23","author":"Karaca","year":"2005","journal-title":"Vaccine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"12497","DOI":"10.1128\/JVI.78.22.12497-12507.2004","article-title":"ChimeriVax-West Nile virus live-attenuated vaccine: Preclinical evaluation of safety, immunogenicity, and efficacy","volume":"78","author":"Arroyo","year":"2004","journal-title":"J. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6694","DOI":"10.1073\/pnas.0601932103","article-title":"A live, attenuated recombinant West Nile virus vaccine","volume":"103","author":"Monath","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/infdis\/jiq003","article-title":"Phase II, randomized, double-blind, placebo-controlled, multicenter study to investigate the immunogenicity and safety of a West Nile virus vaccine in healthy adults","volume":"203","author":"Biedenbender","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1016\/j.vaccine.2012.08.063","article-title":"Risi, Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults \u2265 50 years of age","volume":"30","author":"Dayan","year":"2012","journal-title":"Vaccine"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1016\/j.vaccine.2005.07.002","article-title":"Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines","volume":"23","author":"Hombach","year":"2005","journal-title":"Vaccine"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1128\/JVI.75.9.4268-4275.2001","article-title":"Mutational evidence for an internal fusion peptide in flavivirus envelope protein E","volume":"75","author":"Allison","year":"2001","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0042-6822(03)00450-1","article-title":"Molecularly engineered live-attenuated chimeric West Nile\/dengue virus vaccines protect rhesus monkeys from West Nile virus","volume":"314","author":"Pletnev","year":"2003","journal-title":"Virology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5772","DOI":"10.1016\/j.vaccine.2013.07.064","article-title":"The live attenuated chimeric vaccine rWN\/DEN4Delta30 is well-tolerated and immunogenic in healthy flavivirus-naive adult volunteers","volume":"31","author":"Durbin","year":"2013","journal-title":"Vaccine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/infdis\/jiw501","article-title":"A Live Attenuated Chimeric West Nile Virus Vaccine, rWN\/DEN4Delta30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers","volume":"215","author":"Pierce","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11800","DOI":"10.1128\/JVI.05237-11","article-title":"A fusion-loop antibody enhances the infectious properties of immature flavivirus particles","volume":"85","author":"Moesker","year":"2011","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"175","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":"ref_104","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/icb.1963.2","article-title":"Studies of arthropod-borne virus infections in Queensland. III. Isolation and characterization of virus strains from wild-caught mosquitoes in North Queensland","volume":"41","author":"Doherty","year":"1963","journal-title":"Aust. J. Exp. Biol. Med. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"952","DOI":"10.4269\/ajtmh.2011.11-0165","article-title":"West nile virus (Kunjin subtype) disease in the northern territory of Australia\u2014A case of encephalitis and review of all reported cases","volume":"85","author":"Gray","year":"2011","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1128\/JVI.02903-12","article-title":"A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal West Nile virus infection in aged mice","volume":"87","author":"Pinto","year":"2013","journal-title":"J. Virol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.vaccine.2016.11.080","article-title":"Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine","volume":"35","author":"Poore","year":"2017","journal-title":"Vaccine"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12985-015-0282-8","article-title":"The efficacy of inactivated West Nile vaccine (WN-VAX) in mice and monkeys","volume":"12","author":"Muraki","year":"2015","journal-title":"Virol. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/nm.2763","article-title":"Development of a new hydrogen peroxide-based vaccine platform","volume":"18","author":"Amanna","year":"2012","journal-title":"Nat. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41392-023-01557-7","article-title":"Vaccine adjuvants: Mechanisms and platforms","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1086\/523650","article-title":"A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial","volume":"196","author":"Martin","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_112","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_113","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1086\/509259","article-title":"Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine","volume":"194","author":"Graham","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1016\/j.vaccine.2007.02.050","article-title":"Phase I clinical evaluation of a six-plasmid multiclade HIV-1 DNA candidate vaccine","volume":"25","author":"Catanzaro","year":"2007","journal-title":"Vaccine"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1086\/590434","article-title":"Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: A randomized controlled trial","volume":"198","author":"Holland","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1711088","DOI":"10.3389\/fmicb.2025.1711088","article-title":"Innate immune sensing and vaccine strategies against West Nile virus: Role of Toll-like receptors and viral evasion mechanisms","volume":"16","author":"Kayesh","year":"2025","journal-title":"Front. Microbiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"192","DOI":"10.4103\/2230-973X.167662","article-title":"Needle free injection technology: A complete insight","volume":"5","author":"Ravi","year":"2015","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1128\/CVI.00119-09","article-title":"Immunogenicity and protective efficacy of a recombinant subunit West Nile virus vaccine in rhesus monkeys","volume":"16","author":"Lieberman","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1128\/JVI.01886-10","article-title":"Immunodominance and functional activities of antibody responses to inactivated West Nile virus and recombinant subunit vaccines in mice","volume":"85","author":"Zlatkovic","year":"2011","journal-title":"J. Virol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1016\/j.vaccine.2016.09.044","article-title":"Supramolecular peptide hydrogel adjuvanted subunit vaccine elicits protective antibody responses against West Nile virus","volume":"34","author":"Friedrich","year":"2016","journal-title":"Vaccine"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/1743-422X-7-146","article-title":"A VLP-based vaccine targeting domain III of the West Nile virus E protein protects from lethal infection in mice","volume":"7","author":"Spohn","year":"2010","journal-title":"Virol. J."},{"key":"ref_122","first-page":"1750","article-title":"Immunity to intestinal parasites: Role of mast cells and goblet cells","volume":"42","author":"Levy","year":"1983","journal-title":"Fed. Proc."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.vaccine.2013.01.012","article-title":"A comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen","volume":"31","author":"Gwinn","year":"2013","journal-title":"Vaccine"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.4049\/jimmunol.1203420","article-title":"Innate immunity and its regulation by mast cells","volume":"190","author":"Abraham","year":"2013","journal-title":"J. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"122658","DOI":"10.1016\/j.ijpharm.2023.122658","article-title":"Delivery of small molecule mast cell activators for West Nile Virus vaccination using acetalated dextran microparticles","volume":"634","author":"Hendy","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.xphs.2023.11.025","article-title":"Immunoinformatics-Driven Strategies for Advancing Epitope-Based Vaccine Design for West Nile Virus","volume":"113","author":"Windah","year":"2024","journal-title":"J. Pharm. Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1395870","DOI":"10.3389\/fimmu.2024.1395870","article-title":"Immunoinformatics assisted profiling of West Nile virus proteome to determine immunodominant epitopes for the development of next-generation multi-peptide vaccine","volume":"15","author":"Karkashan","year":"2024","journal-title":"Front. Immunol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"920","DOI":"10.3201\/eid1705.101759","article-title":"Genetic characterization of West Nile virus lineage 2, Greece, 2010","volume":"17","author":"Papa","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Veo, C., Della Ventura, C., Moreno, A., Rovida, F., Percivalle, E., Canziani, S., Torri, D., Calzolari, M., Baldanti, F., and Galli, M. (2019). Evolutionary Dynamics of the Lineage 2 West Nile Virus That Caused the Largest European Epidemic: Italy 2011\u20132018. Viruses, 11.","DOI":"10.3390\/v11090814"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3856","DOI":"10.1016\/j.vaccine.2013.06.059","article-title":"Inactivated West Nile Virus (WNV) vaccine, Duvaxyn WNV, protects against a highly neuroinvasive lineage 2 WNV strain in mice","volume":"31","author":"Venter","year":"2013","journal-title":"Vaccine"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Vorovitch, M.F., Tuchynskaya, K.K., Kruglov, Y.A., Peunkov, N.S., Mostipanova, G.F., Kholodilov, I.S., Ivanova, A.L., Fedina, M.P., Gmyl, L.V., and Morozkin, E.S. (2024). An Inactivated West Nile Virus Vaccine Candidate Based on the Lineage 2 Strain. 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