{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:10:10Z","timestamp":1774498210042,"version":"3.50.1"},"reference-count":65,"publisher":"EDP Sciences","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":153,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2022-137661OB-I00"],"award-info":[{"award-number":["PID2022-137661OB-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19CIII\/00023 (MPY 504\/19)"],"award-info":[{"award-number":["PI19CIII\/00023 (MPY 504\/19)"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["MPY509\/19"],"award-info":[{"award-number":["MPY509\/19"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasite"],"accepted":{"date-parts":[[2025,5,3]]},"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>Reverse vaccinology is a time- and cost-effective approach to identify potential vaccinable antigens for further <jats:italic>in vivo<\/jats:italic> experimental validation. Despite its wide application to multiple organisms, the use of <jats:italic>in silico<\/jats:italic> vaccine development tools to parasitic nematodes has been limited. Herein, we have used the rodent hookworm <jats:italic>Nippostrongylus brasiliensis<\/jats:italic> as a mouse model for the human hookworm <jats:italic>Necator americanus<\/jats:italic> to identify potential vaccine candidates against the latter. Our strategy combined advanced bioinformatic evaluations with knowledge-based criteria. A cumulative rating of antigenic properties was performed resulting in a global prioritization scoring for an updated <jats:italic>N. brasiliensis<\/jats:italic> proteome of 22,796 proteins assigned. Evaluation criteria included homology to the human counterpart <jats:italic>N. americanus<\/jats:italic>, absence of mammalian homologs, cellular location by computational predictors, as well as mass spectrometry data, proteolytic activity of the evaluated protein within the parasite, presence of conserved domains, predicted humoral epitopes, and MHC class II epitope population coverage. To assign one global score representing these characteristics, cumulative scoring was performed. This analysis provided a group of 56 potential candidates, including 11 proteins associated with parasite survival and establishment. Remarkably, the second highest score was assigned to an aspartic protease homologous of the <jats:italic>N. americanus<\/jats:italic> vaccine-candidate <jats:italic>Na<\/jats:italic>-APR-1, which supports the relevance of this approach. Allergenicity and toxicity of the selected molecules were also predicted to anticipate side effects of future candidates. This comprehensive approach provides valuable insights for the rational design of new vaccines against <jats:italic>N. americanus<\/jats:italic>, the results of which, however, must be validated <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1051\/parasite\/2025025","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T07:49:31Z","timestamp":1748936971000},"page":"32","source":"Crossref","is-referenced-by-count":1,"title":["Reverse vaccinology for hookworms: a rational selection of vaccinable antigens against parasitic nematodes"],"prefix":"10.1051","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1443-7233","authenticated-orcid":false,"given":"Javier","family":"Sotillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"Quinzo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Jos\u00e9","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio J.","family":"Mart\u00edn-Galiano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"250","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S1473-3099(20)30288-7","volume":"21","author":"Adegnika","year":"2021","journal-title":"Lancet Infectious Diseases"},{"key":"R2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.smim.2014.06.003","volume":"26","author":"Allen","year":"2014","journal-title":"Seminars in Immunology"},{"key":"R3","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1093\/infdis\/jiz528","volume":"221","author":"Bartlett","year":"2020","journal-title":"Journal of Infectious Diseases"},{"key":"R4","doi-asserted-by":"crossref","first-page":"e1006931","DOI":"10.1371\/journal.ppat.1006931","volume":"14","author":"Bouchery","year":"2018","journal-title":"PLoS Pathogens"},{"key":"R5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/1471-2105-7-153","volume":"7","author":"Bui","year":"2006","journal-title":"BMC Bioinformatics"},{"issue":"12","key":"R6","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/S1473-3099(21)00153-5","volume":"21","author":"Chapman","year":"2021","journal-title":"Lancet Infectious Diseases"},{"key":"R7","doi-asserted-by":"crossref","first-page":"e4497","DOI":"10.1002\/pro.4497","volume":"31","author":"Clifford","year":"2022","journal-title":"Protein Science"},{"key":"R8","doi-asserted-by":"crossref","first-page":"104545","DOI":"10.1016\/j.micpath.2020.104545","volume":"152","author":"Culma","year":"2021","journal-title":"Microbial Pathogenesis"},{"key":"R9","doi-asserted-by":"crossref","first-page":"109639","DOI":"10.1016\/j.intimp.2022.109639","volume":"115","author":"Das","year":"2023","journal-title":"International Immunopharmacology"},{"key":"R10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.meegid.2013.08.007","volume":"20","author":"De Oliveira Lopes","year":"2013","journal-title":"Infection, Genetics and Evolution"},{"key":"R11","unstructured":"Diemert D. 2017. Phase 2 study to assess the safety, efficacy and immunogenicity of Na-GST-1\/alhydrogel co-administered with different toll-like receptor agonists in hookworm-na\u00efve adults. George Washington University, National Institute of Allergy and Infectious Diseases (NIAID). Available at https:\/\/clinicaltrials.gov\/study\/NCT03172975 (accessed 3\/1\/2024)."},{"key":"R12","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jaci.2012.04.027","volume":"130","author":"Diemert","year":"2012","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"R13","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.3389\/fimmu.2017.01763","volume":"8","author":"Dikhit","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"R14","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1471-2105-14-S6-S4","volume":"14","author":"Dimitrov","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"R15","doi-asserted-by":"crossref","first-page":"e0007455","DOI":"10.1371\/journal.pntd.0007455","volume":"13","author":"Donohue","year":"2019","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"R16","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/imcb.12171","volume":"96","author":"Eichenberger","year":"2018","journal-title":"Immunology and Cell Biology"},{"key":"R17","doi-asserted-by":"crossref","first-page":"1014198","DOI":"10.3389\/fvets.2022.1014198","volume":"9","author":"Evangelista","year":"2022","journal-title":"Frontiers in Veterinary Science"},{"key":"R18","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.1038\/s41598-023-30445-x","volume":"13","author":"Evangelista","year":"2023","journal-title":"Scientific Reports"},{"key":"R19","doi-asserted-by":"crossref","first-page":"2.14.1","DOI":"10.1002\/0471140864.ps0214s66","volume":"66","author":"Ezkurdia","year":"2011","journal-title":"Current Protocols in Protein Science"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A. 2005. Protein identification and analysis tools on the ExPASy server, in The Proteomics Protocols Handbook, Walker JM, Editor, Humana Press: Totowa, NJ. p. 571\u2013607.","DOI":"10.1385\/1-59259-890-0:571"},{"key":"R21","unstructured":"Ghodeif AO, Jain H. 2021. Hookworm, in: StatPearls, StatPearls Publishing, Treasure Island, FL, p. 1\u20137."},{"key":"R22","doi-asserted-by":"crossref","first-page":"fuad004","DOI":"10.1093\/femsre\/fuad004","volume":"47","author":"Goodswen","year":"2023","journal-title":"FEMS Microbiology Reviews"},{"key":"R23","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00251-011-0513-0","volume":"63","author":"Greenbaum","year":"2011","journal-title":"Immunogenetics"},{"key":"R24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/bioinformatics\/btaa1102","volume":"37","author":"Hon","year":"2021","journal-title":"Bioinformatics"},{"key":"R25","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJMra032492","volume":"351","author":"Hotez","year":"2004","journal-title":"New England Journal of Medicine"},{"key":"R26","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molbiopara.2016.11.005","volume":"215","author":"Howe","year":"2017","journal-title":"Molecular and Biochemical Parasitology"},{"key":"R27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/nar\/gkg010","volume":"31","author":"Ivanciuc","year":"2003","journal-title":"Nucleic Acids Research"},{"key":"R28","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1093\/bioinformatics\/18.10.1358","volume":"18","author":"Ivanciuc","year":"2002","journal-title":"Bioinformatics"},{"key":"R29","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/imm.12889","volume":"154","author":"Jensen","year":"2018","journal-title":"Immunology"},{"key":"R30","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"R31","doi-asserted-by":"crossref","unstructured":"Knox D.. 2011. Proteases in blood-feeding nematodes and their potential as vaccine candidates, in Cysteine Proteases of Pathogenic Organisms, Robinson MW, Dalton JP, Editors. Springer US: Boston, MA, p. 155\u2013176.","DOI":"10.1007\/978-1-4419-8414-2_10"},{"key":"R32","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.2174\/138161209789105162","volume":"15","author":"Lafuente","year":"2009","journal-title":"Current Pharmaceutical Design"},{"key":"R33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pntd.0008237","volume":"14","author":"Logan","year":"2020","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"R34","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1089\/omi.2010.0150","volume":"15","author":"Loukas","year":"2011","journal-title":"OMICS: A Journal of Integrative Biology"},{"key":"R35","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.ijpara.2021.11.001","volume":"51","author":"Loukas","year":"2021","journal-title":"International Journal for Parasitology"},{"key":"R36","doi-asserted-by":"crossref","first-page":"e45974","DOI":"10.1371\/journal.pone.0045974","volume":"7","author":"Marcilla","year":"2012","journal-title":"PLoS One"},{"key":"R37","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Research"},{"key":"R38","doi-asserted-by":"crossref","first-page":"639573","DOI":"10.3389\/fcimb.2021.639573","volume":"11","author":"Monta\u00f1o","year":"2021","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"key":"R39","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/imm.12601","volume":"148","author":"Nair","year":"2016","journal-title":"Immunology"},{"key":"R40","doi-asserted-by":"crossref","first-page":"e1000107","DOI":"10.1371\/journal.pcbi.1000107","volume":"4","author":"Nielsen","year":"2008","journal-title":"PLoS Computational Biology"},{"key":"R41","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1645\/21-33","volume":"108","author":"Okakpu","year":"2022","journal-title":"Journal of Parasitology"},{"key":"R42","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s12010-016-2048-1","volume":"179","author":"Oliveira","year":"2016","journal-title":"Applied Biochemistry and Biotechnology"},{"key":"R43","doi-asserted-by":"crossref","first-page":"711650","DOI":"10.3389\/fimmu.2021.711650","volume":"12","author":"Perera","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"R44","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1126\/science.287.5459.1816","volume":"287","author":"Pizza","year":"2000","journal-title":"Science"},{"key":"R45","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1186\/s12859-019-3052-6","volume":"20","author":"Quinzo","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"R46","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1369-5274(00)00119-3","volume":"3","author":"Rappuoli","year":"2000","journal-title":"Current Opinion in Microbiology"},{"key":"R47","doi-asserted-by":"crossref","first-page":"W138","DOI":"10.1093\/nar\/gki357","volume":"33","author":"Reche","year":"2005","journal-title":"Nucleic Acids Research"},{"key":"R48","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"R49","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/protein\/12.2.85","volume":"12","author":"Rost","year":"1999","journal-title":"Protein Engineering, Design and Selection"},{"key":"R50","doi-asserted-by":"crossref","first-page":"e14383","DOI":"10.1111\/cbdd.14383","volume":"103","author":"Saravanan","year":"2024","journal-title":"Chemical Biology & Drug Design"},{"key":"R51","doi-asserted-by":"crossref","first-page":"863172","DOI":"10.3389\/falgy.2022.863172","volume":"3","author":"Schein","year":"2022","journal-title":"Frontiers in Allergy"},{"key":"R52","doi-asserted-by":"crossref","first-page":"bbac174","DOI":"10.1093\/bib\/bbac174","volume":"23","author":"Sharma","year":"2022","journal-title":"Briefings in Bioinformatics"},{"key":"R53","doi-asserted-by":"crossref","first-page":"bbaa294","DOI":"10.1093\/bib\/bbaa294","volume":"22","author":"Sharma","year":"2021","journal-title":"Briefings in Bioinformatics"},{"key":"R54","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1074\/mcp.M114.038950","volume":"13","author":"Sotillo","year":"2014","journal-title":"Molecular and Cellular Proteomics"},{"key":"R55","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41587-021-01156-3","volume":"40","author":"Teufel","year":"2022","journal-title":"Nature Biotechnology"},{"key":"R56","doi-asserted-by":"crossref","first-page":"979491","DOI":"10.3389\/fimmu.2022.979491","volume":"13","author":"Thuma","year":"2022","journal-title":"Frontiers in Immunology"},{"key":"R57","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jmb.2003.08.057","volume":"333","author":"Tian","year":"2003","journal-title":"Journal of Molecular Biology"},{"key":"R58","unstructured":"Wadhwa R, Al Amin ASM, Wadhwa R. 2021. Helminthiasis, in StatPearls, StatPearls Publishing: Treasure Island, FL, p. 1\u201311."},{"key":"R59","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1186\/1471-2105-11-568","volume":"11","author":"Wang","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"R60","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1186\/s13071-016-1795-8","volume":"9","author":"Wei","year":"2016","journal-title":"Parasites & Vectors"},{"key":"R61","doi-asserted-by":"crossref","first-page":"106796","DOI":"10.1016\/j.actatropica.2022.106796","volume":"239","author":"Wong","year":"2023","journal-title":"Acta Tropica"},{"key":"R62","unstructured":"World Health Organization. 2020. Ending the neglect to attain the sustainable development goals a road map for neglected tropical diseases 2021\u20132030. World Health Organization. Available at https:\/\/iris.who.int\/handle\/10665\/338565."},{"key":"R63","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1128\/IAI.00848-09","volume":"78","author":"Zhan","year":"2010","journal-title":"Infection and Immunity"},{"key":"R64","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.micinf.2011.03.005","volume":"13","author":"Zhao","year":"2011","journal-title":"Microbes and Infection"},{"key":"R65","doi-asserted-by":"crossref","first-page":"A12","DOI":"10.1136\/bmjgh-2019-EDC.28","volume":"4","author":"Zinsou","year":"2019","journal-title":"BMJ Global Health"}],"container-title":["Parasite"],"original-title":[],"link":[{"URL":"https:\/\/www.parasite-journal.org\/10.1051\/parasite\/2025025\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T07:49:42Z","timestamp":1748936982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.parasite-journal.org\/10.1051\/parasite\/2025025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":65,"alternative-id":["parasite240215"],"URL":"https:\/\/doi.org\/10.1051\/parasite\/2025025","relation":{},"ISSN":["1776-1042"],"issn-type":[{"value":"1776-1042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]}}}