{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:38:31Z","timestamp":1773175111145,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n, Agencia Estatal de Investigaci\u00f3n MCIN\/ AEI \/ 10.13039\/501100011033","award":["PID2020-11919JRJ-100"],"award-info":[{"award-number":["PID2020-11919JRJ-100"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n, Agencia Estatal de Investigaci\u00f3n MCIN\/ AEI \/ 10.13039\/501100011033","award":["PID2019-105117RR-C21"],"award-info":[{"award-number":["PID2019-105117RR-C21"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n, Agencia Estatal de Investigaci\u00f3n MCIN\/ AEI \/ 10.13039\/501100011033","award":["E-RTA-2017-00003-C03"],"award-info":[{"award-number":["E-RTA-2017-00003-C03"]}]},{"DOI":"10.13039\/501100006541","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["P2018\/BAA-4370 PLATESA2-CM"],"award-info":[{"award-number":["P2018\/BAA-4370 PLATESA2-CM"]}],"id":[{"id":"10.13039\/501100006541","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2013-45232-R"],"award-info":[{"award-number":["SAF2013-45232-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2017-88089-R"],"award-info":[{"award-number":["SAF2017-88089-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain\u2013Barr\u00e9 syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic.<\/jats:p>","DOI":"10.3390\/ph15030354","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T02:56:20Z","timestamp":1647312980000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Low Immune Cross-Reactivity between West Nile Virus and a Zika Virus Vaccine Based on Modified Vaccinia Virus Ankara"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3129-813X","authenticated-orcid":false,"given":"Nereida","family":"Jim\u00e9nez de Oya","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda (CNB), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0847-0977","authenticated-orcid":false,"given":"Ana-Bel\u00e9n","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5036-7607","authenticated-orcid":false,"given":"Estela","family":"Escribano-Romero","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0846-2827","authenticated-orcid":false,"given":"Mariano","family":"Esteban","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda (CNB), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8269-5544","authenticated-orcid":false,"given":"Juan-Carlos","family":"Saiz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-5724","authenticated-orcid":false,"given":"Juan","family":"Garc\u00eda-Arriaza","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda (CNB), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28049 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6015-3613","authenticated-orcid":false,"given":"Miguel A.","family":"Mart\u00edn-Acebes","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"ref_1","first-page":"65","article-title":"Infectious disease in an era of global change","volume":"1","author":"Baker","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Krauer, F., Riesen, M., Reveiz, L., Oladapo, O.T., Martinez-Vega, R., Porgo, T.V., Haefliger, A., Broutet, N.J., and Low, N. (2017). Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barre Syndrome: Systematic Review. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002203"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/gcb.15384","article-title":"Warming temperatures could expose more than 1.3 billion new people to Zika virus risk by 2050","volume":"27","author":"Ryan","year":"2021","journal-title":"Glob. Chang. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1602113","article-title":"Zika Virus","volume":"374","author":"Petersen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/rmv.2145","article-title":"The expanding arms of Zika virus: An updated review with recent Indian outbreaks","volume":"31","author":"Agarwal","year":"2021","journal-title":"Rev. Med. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1016\/S0140-6736(19)32790-4","article-title":"The first local cases of Zika virus in Europe","volume":"394","author":"Brady","year":"2019","journal-title":"Lancet"},{"key":"ref_7","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_8","first-page":"e81","article-title":"Zika virus infection confers protection against West Nile virus challenge in mice","volume":"6","author":"Blazquez","year":"2017","journal-title":"Emerg. Microbes Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00430-020-00658-2","article-title":"The effects of Japanese encephalitis virus antibodies on Zika virus infection","volume":"209","author":"He","year":"2020","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1126\/science.abb6143","article-title":"Zika virus infection enhances future risk of severe dengue disease","volume":"369","author":"Katzelnick","year":"2020","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"572681","DOI":"10.3389\/fcimb.2020.572681","article-title":"Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine","volume":"10","author":"Shukla","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2100","DOI":"10.1002\/rmv.2100","article-title":"The role of anti-flavivirus humoral immune response in protection and pathogenesis","volume":"30","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00011-18","DOI":"10.1128\/mSphereDirect.00011-18","article-title":"Tick-Borne Encephalitis Virus Vaccine-Induced Human Antibodies Mediate Negligible Enhancement of Zika Virus Infection InVitro and in a Mouse Model","volume":"3","author":"Duehr","year":"2018","journal-title":"mSphere"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.vaccine.2018.02.073","article-title":"A plant-produced vaccine protects mice against lethal West Nile virus infection without enhancing Zika or dengue virus infectivity","volume":"36","author":"Lai","year":"2018","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102991","DOI":"10.1016\/j.ebiom.2020.102991","article-title":"Dengue and Zika virus infections are enhanced by live attenuated dengue vaccine but not by recombinant DSV4 vaccine candidate in mouse models","volume":"60","author":"Shukla","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Johnson, N., Fernandez de Marco, M., Giovannini, A., Ippoliti, C., Danzetta, M.L., Svartz, G., Erster, O., Groschup, M.H., Ziegler, U., and Mirazimi, A. (2018). Emerging Mosquito-Borne Threats and the Response from European and Eastern Mediterranean Countries. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15122775"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/14787210.2020.1713751","article-title":"The knowns and unknowns of West Nile virus in Europe: What did we learn from the 2018 outbreak?","volume":"18","author":"Camp","year":"2020","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41598-017-18781-1","article-title":"T cell immunity to Zika virus targets immunodominant epitopes that show cross-reactivity with other Flaviviruses","volume":"8","author":"Reynolds","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e190098","DOI":"10.1590\/0074-02760190098","article-title":"Previous dengue or Zika virus exposure can drive to infection enhancement or neutralisation of other flaviviruses","volume":"114","author":"Oliveira","year":"2019","journal-title":"Mem. Inst. Oswaldo Cruz."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","unstructured":"Garg, H., Yeh, R., Watts, D.M., Mehmetoglu-Gurbuz, T., Resendes, R., Parsons, B., Gonzales, F., and Joshi, A. (2021). Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection. BMC Immunol., 22.","DOI":"10.1186\/s12865-020-00389-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"686411","DOI":"10.3389\/fimmu.2021.686411","article-title":"Evaluating the Safety of West Nile Virus Immunity During Congenital Zika Virus Infection in Mice","volume":"12","author":"Acklin","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17385","DOI":"10.1038\/s41598-018-35724-6","article-title":"A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice","volume":"8","author":"Perez","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1080\/22221751.2021.1951624","article-title":"The combined vaccination protocol of DNA\/MVA expressing Zika virus structural proteins as efficient inducer of T and B cell immune responses","volume":"10","author":"Perez","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/s41467-017-01669-z","article-title":"Dengue virus-reactive CD8(+) T cells mediate cross-protection against subsequent Zika virus challenge","volume":"8","author":"Wen","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lopez-Camacho, C., Kim, Y.C., Abbink, P., Larocca, R.A., Huiskonen, J.T., Barouch, D.H., and Reyes-Sandoval, A. (2019). Assessment of Immunogenicity and Efficacy of a Zika Vaccine Using Modified Vaccinia Ankara Virus as Carriers. Pathogens, 8.","DOI":"10.3390\/pathogens8040216"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3389\/fimmu.2020.00334","article-title":"Cross-Reactive Immunity among Flaviviruses","volume":"11","author":"Rathore","year":"2020","journal-title":"Front. Immunol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/3\/354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:36:32Z","timestamp":1760135792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/3\/354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,15]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ph15030354"],"URL":"https:\/\/doi.org\/10.3390\/ph15030354","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,15]]}}}