{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:05:13Z","timestamp":1788793513544,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["Juan de la Cierva - Incorporaci\u00f3n IJCI-2015-24164"],"award-info":[{"award-number":["Juan de la Cierva - Incorporaci\u00f3n IJCI-2015-24164"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["BIO2014:54164R"],"award-info":[{"award-number":["BIO2014:54164R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RICET - ISCIII RD12\/0018\/0010; FEDER"],"award-info":[{"award-number":["RICET - ISCIII RD12\/0018\/0010; FEDER"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006531","name":"Departament d'Universitats, Recerca i Societat de la Informaci\u00f3","doi-asserted-by":"publisher","award":["AGAUR - 2017SGR00924"],"award-info":[{"award-number":["AGAUR - 2017SGR00924"]}],"id":[{"id":"10.13039\/501100006531","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010552","name":"Departament de Salut, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["PERIS 2016-2010 SLT008\/18\/00132"],"award-info":[{"award-number":["PERIS 2016-2010 SLT008\/18\/00132"]}],"id":[{"id":"10.13039\/501100010552","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>African animal trypanosomiasis is caused by vector-transmitted parasites of the genus Trypanosoma. T. congolense and T. brucei brucei are predominant in Africa; T. evansi and T. vivax in America and Asia. They have in common an extracellular lifestyle and livestock tropism, which provokes huge economic losses in regions where vectors are endemic. There are licensed drugs to treat the infections, but adherence to treatment is poor and appearance of resistances common. Therefore, the availability of a prophylactic vaccine would represent a major breakthrough towards the management and control of the disease. Selection of the most appropriate antigens for its development is a bottleneck step, especially considering the limited resources allocated. Herein we propose a vaccine strategy based on multiple epitopes from multiple antigens to counteract the parasites\u00b4 biological complexity. Epitopes were identified by computer-assisted genome-wide screenings, considering sequence conservation criteria, antigens annotation and sub-cellular localization, high binding affinity to antigen presenting molecules, and lack of cross-reactivity to proteins in cattle and other breeding species. We ultimately provide 31 B-cell, 8 CD4 T-cell, and 15 CD8 T-cell epitope sequences from 30 distinct antigens for the prospective design of a genetic ensemble vaccine against the four trypanosome species responsible for African animal trypanosomiasis.<\/jats:p>","DOI":"10.3390\/vaccines8010130","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T08:13:27Z","timestamp":1584519207000},"page":"130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Design of an Epitope-Based Vaccine Ensemble for Animal Trypanosomiasis by Computational Methods"],"prefix":"10.3390","volume":"8","author":[{"given":"Lucas","family":"Michel-Tod\u00f3","sequence":"first","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic - University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Bigey","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique (CNRS), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 de Paris, UTCBS, F-75006 Paris, France"},{"name":"PSL University, ChimieParisTech, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A","family":"Reche","sequence":"additional","affiliation":[{"name":"Laboratory of Immunomedicine, Faculty of Medicine, University Complutense of Madrid, Ave Complutense S\/N, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Jesus","family":"Pinazo","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic - University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Gasc\u00f3n","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic - University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-7969","authenticated-orcid":false,"given":"Julio","family":"Alonso-Padilla","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic - University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.pt.2016.04.012","article-title":"Animal African trypanosomiasis: Time to increase focus on clinically relevant parasite and host species","volume":"32","author":"Morrison","year":"2016","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/pim.12387","article-title":"Prospects for vaccination against pathogenic African trypanosomes","volume":"38","author":"Black","year":"2016","journal-title":"Parasite Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1002\/eji.1830250725","article-title":"Are CD8 T cells involved in control of African trypanosomiasis in a natural host environment?","volume":"25","author":"Sileghem","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.vetpar.2016.05.003","article-title":"Combatting African animal trypanosomiasis (AAT) in livestock: The potential role of trypanotolerance","volume":"225","author":"Yaro","year":"2016","journal-title":"Vet. Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mekonnen, G., Mohammed, E.F., Kidane, W., Nesibu, A., Yohannes, H., Van Reet, N., B\u00fcscher, P., and Birhanu, H. (2018). Isometamidium chloride and homidium chloride fail to cure mice infected with Ethiopian Trypanosoma evansi type A and B. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006790"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1017\/S0031182010000223","article-title":"Current status of vaccination against African trypanosomiasis","volume":"137","author":"Magez","year":"2010","journal-title":"Parasitology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.4161\/hv.7.11.18203","article-title":"Vaccination against trypanosomiasis: Can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist?","volume":"7","author":"Magez","year":"2011","journal-title":"Hum. Vaccines"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"582","DOI":"10.3389\/fimmu.2017.00582","article-title":"African trypanosomes undermine humoral responses and vaccine development: Link with inflammatory responses?","volume":"8","author":"Stijlemans","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1186\/s13071-015-1189-3","article-title":"Protective antibody and cytokine responses in mice following immunization with recombinant beta-tubulin and subsequent Trypanosoma evansi challenge","volume":"8","author":"Tewari","year":"2015","journal-title":"Parasites Vectors"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.exppara.2010.06.017","article-title":"Trypanosoma brucei: Immunisation with plasmid DNA encoding invariant surface glycoprotein gene is able to induce partial protection in experimental African trypanosomiasis","volume":"127","author":"Atouguia","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0020-7519(97)00154-9","article-title":"Immune responses of cattle to African trypanosomes: Protective or pathogenic?","volume":"28","author":"Taylor","year":"1998","journal-title":"Int. J. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D457","DOI":"10.1093\/nar\/gkp851","article-title":"TriTrypDB: A functional genomic resource for the Trypanosomatidae","volume":"38","author":"Aslett","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1093\/bioinformatics\/btl158","article-title":"Cd-hit: A fast program for clustering and comparing large sets of protein or nucleotide sequences","volume":"22","author":"Li","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: Multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/j.1538-7305.1948.tb01338.x","article-title":"The mathematical theory of commnication","volume":"27","author":"Shannon","year":"1948","journal-title":"Bell Syst. Technol. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0161-5890(97)00130-2","article-title":"A Shannon entropy analysis of immunoglobulin and T cell receptor","volume":"34","author":"Stewart","year":"1997","journal-title":"Mol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"W24","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: Improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"Jespersen","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"W502","DOI":"10.1093\/nar\/gkz452","article-title":"IEDB-AR: Immune epitope database-analysis resource in 2019","volume":"47","author":"Dhanda","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_19","first-page":"e000071","article-title":"Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis","volume":"2","author":"Farrell","year":"2016","journal-title":"Microb. Genom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/s41467-018-03317-6","article-title":"Assembly of 913 microbial genomes from metagenomic sequencing of the cow rumen","volume":"9","author":"Stewart","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/nprot.2007.131","article-title":"Locating proteins in the cell using TargetP, SignalP and related tools","volume":"2","author":"Emanuelsson","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pierleoni, A., Martelli, P., and Casadio, R. (2008). PredGPI: A GPI-anchor predictor. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-392"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/prot.23175","article-title":"RaptorX: Exploiting structure information for protein alignment by statistical inference","volume":"79","author":"Peng","year":"2011","journal-title":"Proteins"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/icb.1997.63","article-title":"Multi-epitope DNA vaccines","volume":"75","author":"Suhrbier","year":"1997","journal-title":"Immunol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8619","DOI":"10.1016\/j.vaccine.2011.09.016","article-title":"Increased survival time in mice vaccinated with a branched lysine multiple antigenic peptide containing B- and T-cell epitopes from T. gondii antigens","volume":"29","author":"Wang","year":"2011","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jri.2008.09.002","article-title":"DNA vaccine encoding chimeric protein encompassing epitopes of human ZP3 and ZP4: Immunogenicity and characterization of antibodies","volume":"79","author":"Choudhury","year":"2009","journal-title":"J. Reprod. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fimmu.2019.00284","article-title":"Prime-boost vaccine regimen for SjTPI and SjC23schistosome vaccines, increase efficacy in water buffalo in a field trial in China","volume":"10","author":"Li","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1046\/j.1365-3083.2003.01218.x","article-title":"DNA injection in combination with electroporation: A novel method for vaccination of farmed ruminants","volume":"57","author":"Tollefsen","year":"2003","journal-title":"Scand. J. Immunol."},{"key":"ref_29","unstructured":"(2019, November 20). Integrated DNA Technologies IDT\u2014Codon Optimization Tool. Available online: https:\/\/eu.idtdna.com\/CodonOpt."},{"key":"ref_30","unstructured":"Stothard, P. (2019, November 20). Sequence Manipulation Suite (SMS): Reverse Translate. Available online: http:\/\/www.bioinformatics.org\/sms2\/rev_trans.html."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1462-5822.2011.01730.x","article-title":"Sialidases play a key role in infection and anaemia in Trypanosoma congolense animal trypanosomiasis","volume":"14","author":"Coustou","year":"2012","journal-title":"Cell. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fpubh.2018.00062","article-title":"Vaccines meet big data: State-of-the-art and future prospects. From the classical 3Is (\u201cisolate-inactivate-inject\u201d) Vaccinology 1.0 to Vaccinology 3.0, vaccinomics, and beyond: A historical overview","volume":"6","author":"Bragazzi","year":"2018","journal-title":"Front. Public Health"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.meegid.2017.04.009","article-title":"Development of a multi-epitope peptide vaccine inducing robust T cell responses against brucellosis using immunoinformatics based approaches","volume":"51","author":"Saadi","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ttbdis.2012.01.003","article-title":"A systematic, functional genomics, and reverse vaccinology approach to the identification of vaccine candidates in the cattle tick, Rhipicephalus microplus","volume":"3","author":"Stutzer","year":"2012","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.3389\/fimmu.2018.02213","article-title":"Immuno-informatics analysis to identify novel vaccine candidates and design of a multi-epitope based vaccine candidate against Theileria parasites","volume":"9","author":"Kar","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ygeno.2018.02.017","article-title":"A comparative in silico linear B-cell epitope prediction and characterization for South American and African Trypanosoma vivax strains","volume":"111","author":"Guedes","year":"2019","journal-title":"Genomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s00251-015-0877-7","article-title":"A modern approach for epitope prediction: Identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules","volume":"67","author":"Pandya","year":"2015","journal-title":"Immunogenetics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1021\/acs.jproteome.7b00675","article-title":"Improved prediction of bovine leucocyte antigens (BoLA) presented ligands by use of mass-spectrometry-determined ligand and in vitro binding data","volume":"17","author":"Nielsen","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zikova, A., Schnaufer, A., Dalley, R.A., Panigrahi, A.K., and Stuart, K.D. (2009). The F(0)F(1)-ATP synthase complex contains novel subunits and is essential for procyclic Trypanosoma brucei. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000436"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1186\/s13071-017-2411-2","article-title":"Molecular prevalence of trypanosome infections in cattle and tsetse flies in the Maasai Steppe, northern Tanzania","volume":"10","author":"Simwango","year":"2017","journal-title":"Parasites Vectors"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1128\/IAI.00729-08","article-title":"T-cell responses to the trypanosome variant surface glycoprotein are not limited to hypervariable subregions","volume":"77","author":"Dagenais","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1086\/503808","article-title":"Interferon-\u03b3 and nitric oxide in combination with antibodies are key protective host immune factors during Trypanosoma congolense Tc13 infections","volume":"193","author":"Magez","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Mansfield, J.M., Paulnock, D.M., and Hedberg, G.M. (2013). Bridging Innate and Adaptive Immunity in African Trypanosomiasis. Trypanosomes and Trypanosomiasis, Springer-Nature.","DOI":"10.1007\/978-3-7091-1556-5_4"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1128\/IAI.00357-15","article-title":"Distinct contributions of CD4+ and CD8+ T cells to pathogenesis of Trypanosoma brucei infection in the context of gamma interferon and interleukin-10","volume":"83","author":"Liu","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0304-4017(00)00273-9","article-title":"Effects of the depletion of CD8+ T cells and monocytes on the proliferative responses of peripheral blood leucocytes from Trypanosoma evansi-infected sheep","volume":"92","author":"Onah","year":"2000","journal-title":"Vet. Parasitol."},{"key":"ref_46","first-page":"639","article-title":"Parasite-specific T-cell responses of trypanotolerant and trypanosusceptible cattle during infection with Trypanosoma congolense","volume":"75","author":"Flynn","year":"1992","journal-title":"Immunology"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Radwanska, M., Guirnalda, P., De Trez, C., Ryffel, B., Black, S., and Magez, S. (2008). Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000078"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.molbiopara.2014.05.001","article-title":"Antigenic variation in African trypanosomes","volume":"195","author":"Horn","year":"2017","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1586\/erv.13.33","article-title":"Synthetic DNA vaccine strategies against persistent viral infections","volume":"12","author":"Villarreal","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ab.2005.08.029","article-title":"Investigations of the effect of DNA size in transient transfection assay using dual luciferase system","volume":"346","author":"Yin","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13567-019-0698-z","article-title":"Recent advances in delivery of veterinary DNA vaccines against avian pathogens","volume":"50","author":"Jazayeri","year":"2019","journal-title":"Vet. Res."},{"key":"ref_52","first-page":"287","article-title":"Minimum dose, antigen content, and immunization duration of a trivalent vaccine of inactivated Haemophilus parasuis serovars 4, 5, and 12 against Gl\u00e4sser\u2019s disease in pigs","volume":"80","author":"Zhao","year":"2016","journal-title":"Can. J. Vet. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tabel, H., Wei, G., and Bull, H.J. (2013). Immunosuppression: Cause for failures of vaccines against African trypanosomiases. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002090"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/bs.adgen.2014.10.003","article-title":"Electroporation-mediated gene delivery","volume":"89","author":"Young","year":"2015","journal-title":"Adv. Genet."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/130\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:07:14Z","timestamp":1760173634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,16]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["vaccines8010130"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8010130","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,16]]}}}