{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:51:30Z","timestamp":1792511490525,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Vaccines"],"abstract":"<jats:p>Zika virus (ZIKV) is a flavivirus similar to Dengue virus (DENV) in terms of transmission and clinical manifestations, and usually both viruses are found to co-circulate. ZIKV is usually transmitted by mosquitoes bites, but may also be transmitted by blood transfusion, via the maternal\u2013foetal route, and sexually. After 2015, when the most extensive outbreak of ZIKV had occurred in Brazil and subsequently spread throughout the rest of South America, it became evident that ZIKV infection during the first trimester of pregnancy was associated with microcephaly and other neurological complications in newborns. As a result, the development of a vaccine against ZIKV became an urgent goal. A major issue with DENV vaccines, and therefore likely also with ZIKV vaccines, is the induction of antibodies that fail to neutralize the virus properly and cause antibody-dependent enhancement (ADE) of the infection instead. It has previously been shown that antibodies against the third domain of the envelope protein (EDIII) induces optimally neutralizing antibodies with no evidence for ADE for other viral strains. Therefore, we generated a ZIKV vaccine based on the EDIII domain displayed on the immunologically optimized Cucumber mosaic virus (CuMVtt) derived virus-like particles (VLPs) formulated in dioleoyl phosphatidylserine (DOPS) as adjuvant. The vaccine induced high levels of specific IgG after a single injection. The antibodies were able to neutralise ZIKV without enhancing infection by DENV in vitro. Thus, the here described vaccine based on EDIII displayed on VLPs was able to stimulate production of antibodies specifically neutralizing ZIKV without potentially enhancing disease caused by DENV.<\/jats:p>","DOI":"10.3390\/vaccines7030072","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T10:44:51Z","timestamp":1563878691000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection"],"prefix":"10.3390","volume":"7","author":[{"given":"Gustavo","family":"Cabral-Miranda","sequence":"first","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology (CCMP), University of Oxford, Oxford OX1 2JD, UK"},{"name":"Immunology, RIA, Inselspital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Lim","sequence":"additional","affiliation":[{"name":"Artemis Bio-Support, Molengraaffsingel, 2629 Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3510-9148","authenticated-orcid":false,"given":"Mona O.","family":"Mohsen","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology (CCMP), University of Oxford, Oxford OX1 2JD, UK"},{"name":"Immunology, RIA, Inselspital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya V.","family":"Pobelov","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa S.","family":"Roesti","sequence":"additional","affiliation":[{"name":"Immunology, RIA, Inselspital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Heath","sequence":"additional","affiliation":[{"name":"Bencard Adjuvant Systems, Worthing BN14 8SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray A.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Bencard Adjuvant Systems, Worthing BN14 8SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-4733","authenticated-orcid":false,"given":"Matthias F.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Bencard Adjuvant Systems, Worthing BN14 8SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron E. E.","family":"Martina","sequence":"additional","affiliation":[{"name":"Artemis Bio-Support, Molengraaffsingel, 2629 Delft, The Netherlands"},{"name":"Department of Viroscience, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-2099","authenticated-orcid":false,"given":"Martin F.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology (CCMP), University of Oxford, Oxford OX1 2JD, UK"},{"name":"Immunology, RIA, Inselspital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2019, February 25). Zika Virus. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/zika\/en\/."},{"key":"ref_2","unstructured":"European Centre for Disease Prevention and Control (2016). Zika Virus Disease Epidemic: Preparedness Planning Guide for Diseases Transmitted by Aedes Aegypti and Aedes Albopictus, ECDC."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1016\/S0140-6736(16)30775-9","article-title":"Late sexual transmission of Zika virus related to persistence in the semen","volume":"387","author":"Turmel","year":"2016","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S1473-3099(16)30153-0","article-title":"Zika virus in semen of a patient returning from a non-epidemic area","volume":"16","author":"Mansuy","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s13669-016-0171-1","article-title":"The Zika Virus and Pregnancy","volume":"5","author":"Fiorentino","year":"2016","journal-title":"Curr. Obstet. Gynecol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/S0140-6736(16)30428-7","article-title":"Zika virus: A new challenge for blood transfusion","volume":"387","author":"Musso","year":"2016","journal-title":"Lancet"},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0140-6736(16)00320-2","article-title":"Zika virus and microcephaly: Why is this situation a PHEIC?","volume":"387","author":"Heymann","year":"2016","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13690-017-0233-5","article-title":"Zika virus disease, microcephaly and Guillain-Barr\u00e9 syndrome in Colombia: Epidemiological situation during 21 months of the Zika virus outbreak, 2015\u20132017","volume":"75","author":"Mattar","year":"2017","journal-title":"Arch. Public Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bjid.2018.02.005","article-title":"Prevalence of Guillain-Barr\u00e9 syndrome among Zika virus infected cases: A systematic review and meta-analysis","volume":"22","author":"Barbi","year":"2018","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Styczynski, A.R., Malta, J.M.A.S., Krow-Lucal, E.R., Percio, J., Nobrega, M.E., Vargas, A., Lanzieri, T.M., Leite, P.L., Staples, J.E., and Fischer, M.X. (2017). Increased rates of Guillain-Barre\u2019 syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005869"},{"key":"ref_12","unstructured":"(2019, March 04). WHO Statement on the First Meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on Zika Virus and Observed Increase in Neurological Disorders and Neonatal Malformations. Available online: https:\/\/www.who.int\/news-room\/detail\/01-02-2016-who-statement-on-the-first-meeting-of-the-international-health-regulations-(2005)-(ihr-2005)-emergency-committee-on-zika-virus-and-observed-increase-in-neurological-disorders-and-neonatal-malformations."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/s41467-019-09391-8","article-title":"Structure mapping of dengue and Zika viruses reveals functional long-range interactions","volume":"10","author":"Huber","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/ni.3515","article-title":"Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus","volume":"17","author":"Dejnirattisai","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7852","DOI":"10.1073\/pnas.1607931113","article-title":"Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus","volume":"113","author":"Priyamvada","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1093\/infdis\/jiw377","article-title":"Zika Virus-Induced Antibody Response Enhances Dengue Virus Serotype 2 Replication In Vitro","volume":"214","author":"Kawiecki","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fcimb.2018.00044","article-title":"Antibody-Dependent Enhancement and Zika: Real Threat or Phantom Menace?","volume":"8","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1126\/science.1185181","article-title":"Cross-reacting antibodies enhance dengue virus infection in humans","volume":"328","author":"Dejnirattisai","year":"2010","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection","volume":"353","author":"Stettler","year":"2016","journal-title":"Science"},{"key":"ref_20","first-page":"781","article-title":"Dengue virus (DENV)-specific antibodies enhance Brazilian Zika virus (ZIKV) infection","volume":"215","author":"Castanha","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3389\/fimmu.2018.00597","article-title":"Modulation of Dengue\/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection","volume":"9","author":"Khandia","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41541-018-0061-9","article-title":"Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation","volume":"3","author":"Barrett","year":"2018","journal-title":"NPJ Vaccines"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Makhluf, H., and Shresta, S. (2018). Development of Zika Virus Vaccines. Vaccines, 6.","DOI":"10.3390\/vaccines6010007"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.coi.2018.04.024","article-title":"Zika virus vaccines: Immune response, current status, and future challenges","volume":"53","author":"Richner","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ejim.2017.08.001","article-title":"Current status of therapeutic and vaccine approaches against Zika virus","volume":"44","author":"Wahid","year":"2017","journal-title":"Eur J. Intern. Med."},{"key":"ref_26","first-page":"48","article-title":"Structural basis of potent Zika-dengue virus antibody cross-neutralization","volume":"53","author":"Dejnirattisai","year":"2016","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4110\/in.2015.15.2.51","article-title":"Recent Advances of Vaccine Adjuvants for Infectious Diseases","volume":"15","author":"Lee","year":"2015","journal-title":"Immune Netw."},{"key":"ref_28","first-page":"407","article-title":"Adjuvants are key factors for the development of future vaccines:lessons from the Finlay adjuvant platform","volume":"4","author":"Romeu","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.4049\/jimmunol.1400065","article-title":"Viral Particles Drive Rapid Differentiation of Memory B Cells into Secondary Plasma Cells Producing Increased Levels of Antibodies","volume":"192","author":"Zabel","year":"2014","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.smim.2017.08.014","article-title":"Major findings and recent advances in virus-like particle (VLP)-based vaccines","volume":"34","author":"Mohsen","year":"2017","journal-title":"Semin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41541-017-0030-8","article-title":"Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer\u2019s and cat allergy","volume":"2","author":"Zeltins","year":"2017","journal-title":"NPJ Vaccines"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.4049\/jimmunol.0903949","article-title":"Cutting edge: IL-21 and TLR signaling regulate germinal center responses in a B cell-intrinsic manner","volume":"184","author":"Bessa","year":"2010","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"736","DOI":"10.3389\/fimmu.2019.00736","article-title":"RNA and Toll-Like Receptor 7 License the Generation of Superior Secondary Plasma Cells at Multiple Levels in a B Cell Intrinsic Fashion","volume":"10","author":"Krueger","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_34","first-page":"456","article-title":"Phosphatidyl serine (PS) derivatives alter immune responses in a brown Norway rat model of allergic sensitisation","volume":"62","author":"Dixon","year":"2007","journal-title":"Allergy"},{"key":"ref_35","unstructured":"Berry, A.R., and Wheeler, A.W. (2004). Composition Comprising Phosphatidyl Serine and an Antigen or Allergen and the Use Thereof. (US 8,765,721 B2), U.S. Patent."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cabral-Miranda, G., Salman, A.M., Mohsen, M.O., Storni, F.L., Roesti, E.S., Skinner, M.A., Heath, M.D., Kramer, M.F., Khan, S.M., and Janse, C.J. (2018). DOPS Adjuvant Confers Enhanced Protection against Malaria for VLP-TRAP Based Vaccines. Diseases, 6.","DOI":"10.3390\/diseases6040107"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bios.2018.04.058","article-title":"Biosensor-based selective detection of Zika virus specific antibodies in infected individuals","volume":"113","author":"Cardoso","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Cabral-Miranda, G., Heath, M.D., Mohsen, M.O., Gomes, A.C., Engeroff, P., Flaxman, A., Leoratti, F.M.S., El-Turabi, A., Reyes-Sandoval, A., and Skinner, M.A. (2017). Virus-Like Particle (VLP) Plus Microcrystalline Tyrosine (MCT) Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei\/vivax. Vaccines, 5.","DOI":"10.3390\/vaccines5020010"},{"key":"ref_39","first-page":"30159","article-title":"Isolation of infectious Zika virus from saliva and prolonged viral RNA shedding in a traveller returning from the Dominican Republic to Italy, January 2016","volume":"21","author":"Barzon","year":"2016","journal-title":"Eurosurveillance"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1128\/JCM.01294-08","article-title":"Pan-dengue virus detection by PCR for travelers returning from the tropics","volume":"46","author":"Dumoulin","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1128\/JCM.40.7.2323-2330.2002","article-title":"Rapid Detection and Quantification of RNA of Ebola and Marburg Viruses, Lassa Virus, Crimean-Congo Hemorrhagic Fever Virus, Rift Valley Fever Virus, Dengue Virus, and Yellow Fever Virus by Real-Time Reverse Transcription-PCR","volume":"40","author":"Drosten","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"45505","DOI":"10.1038\/srep45505","article-title":"Global evolutionary history and spatio-temporal dynamics of dengue virus type 2","volume":"7","author":"Wie","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ijc.2910260208","article-title":"Establishment and characterization of a human acute monocytic leukemia cell line (THP-1)","volume":"26","author":"Tsuchiya","year":"1980","journal-title":"Int. J. Cancer"},{"key":"ref_45","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_46","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_47","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.chom.2018.10.008","article-title":"Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages","volume":"24","author":"Zimmerman","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.1016\/S1473-3099(18)30063-X","article-title":"Development of vaccines against Zika virus","volume":"18","author":"Poland","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7679","DOI":"10.1038\/s41598-017-08247-9","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_50","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1128\/IAI.68.4.2102-2109.2000","article-title":"Linkage of exogenous T-cell epitopes to the 19-kilodalton region of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) can enhance protective immunity against malaria and modulate the immunoglobulin subclass response to MSP1(19)","volume":"68","author":"Ahlborg","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.chom.2007.09.015","article-title":"Complement protein C1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner","volume":"2","author":"Mehlhop","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.chom.2010.07.007","article-title":"Direct complement restriction of flavivirus infection requires glycan recognition by mannose-binding lectin","volume":"8","author":"Fuchs","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e00276-11","DOI":"10.1128\/mBio.00276-11","article-title":"Complement-mediated neutralization of dengue virus requires mannose-binding lectin","volume":"2","author":"Avirutnan","year":"2011","journal-title":"MBio"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Suppiah, J., Ching, S.M., Amin-Nordin, S., Mat-Nor, L.A., Ahmad-Najimudin, N.A., Low, G.K., Abdul-Wahid, M.Z., Thayan, R., and Chee, H.Y. (2018). Clinical manifestations of dengue in relation to dengue serotype and genotype in Malaysia: A retrospective observational study. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006817"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.celrep.2018.10.006","article-title":"Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization","volume":"25","author":"Gallichotte","year":"2018","journal-title":"Cell Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1126\/scitranslmed.3003084","article-title":"Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity","volume":"3","author":"OhAinle","year":"2011","journal-title":"Sci. Transl. Med."}],"updated-by":[{"DOI":"10.3390\/vaccines8010094","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000}}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/72\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T22:30:45Z","timestamp":1754260245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/72"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,23]]},"references-count":56,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["vaccines7030072"],"URL":"https:\/\/doi.org\/10.3390\/vaccines7030072","relation":{"correction":[{"id-type":"doi","id":"10.3390\/vaccines8010094","asserted-by":"object"}]},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,23]]}}}