{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:32:51Z","timestamp":1787841171798,"version":"build-2784847793"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>\n                      Cutaneous leishmaniasis poses significant health and socioeconomic challenges, making vaccine development a top priority, especially in endemic regions. Cysteine proteases, KMP-11, and HASPB proteins are promising candidates for leishmaniasis vaccine development owing to their immunogenic properties and capacity to provoke robust immune responses, as evidenced by different investigations. This study aimed to design a recombinant chimeric protein (MEV-Fc) vaccine using multi-epitopes from these\n                      <jats:italic toggle=\"yes\">Leishmania major<\/jats:italic>\n                      proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>The antigens were subjected to immunoinformatic prediction and screening of HTL, CTL, and B-cell epitopes. The multi-epitope protein was designed with significantly high-scoring epitopes and suitable linkers. Natural adjuvants were then added to enhance immunogenicity. Vaccine potency was innovatively improved by covalently fusing human IgG1 Fc with multi-epitope protein. To investigate how the MEV-Fc vaccine interacts with Toll-like receptors, molecular docking, multi-scale normal mode analysis simulation, and computational immune simulation were employed to study humoral and cellular immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings\/Results:<\/jats:title>\n                    <jats:p>The results demonstrated the vaccine\u2019s antigenicity, stability, and nontoxicity. The structural validation confirmed the accuracy of the 3D models, indicating robust interactions with TLR2 and TLR4, with binding free energies of -1269.9 and -1128.7 (kcal\/mol), respectively. Immune simulation results showed significant increases in IgM and IgG antibody levels following three vaccinations, along with enhanced activation of B cells, helper T cells, and cytotoxic T lymphocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications:<\/jats:title>\n                    <jats:p>These findings provide novel insights for developing effective candidates for cutaneous leishmaniasis vaccines. However, laboratory experiments are necessary to evaluate its protective effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/rps.rps_145_24","type":"journal-article","created":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T01:00:17Z","timestamp":1734224417000},"page":"729-745","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Immunoinformatic approach to the design of a novel multi-epitope vaccine against Leishmania major fused to human IgG-Fc"],"prefix":"10.4103","volume":"19","author":[{"given":"Mahmood","family":"Fadaie","sequence":"first","affiliation":[{"name":"Skin Diseases and Leishmaniasis Research Center, Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zabihollah","family":"Shahmoradi","sequence":"additional","affiliation":[{"name":"Skin Diseases and Leishmaniasis Research Center, Department of Dermatology, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Khanahmad","sequence":"additional","affiliation":[{"name":"Skin Diseases and Leishmaniasis Research Center, Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,12,15]]},"reference":[{"issue":"6","key":"R1-20241215","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s40257-022-00726-8","article-title":"Cutaneous leishmaniasis: a 2022 updated narrative review into diagnosis and management developments","volume":"23","author":"de Vries","year":"2022","journal-title":"Am J Clin Dermatol"},{"issue":"5","key":"R2-20241215","doi-asserted-by":"crossref","first-page":"e0009373","DOI":"10.1371\/journal.pntd.0009373","article-title":"New global targets for NTDs in the WHO roadmap 2021\u20132030","volume":"15","author":"Casulli","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"R3-20241215","doi-asserted-by":"crossref","first-page":"e0295495","DOI":"10.1371\/journal.pone.0295495","article-title":"Designing of a new multi-epitope vaccine against Leishmania major using Leish-F1 epitopes: An in-silico study","volume":"19","author":"Rabienia","year":"2024","journal-title":"PLoS One"},{"issue":"4","key":"R4-20241215","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4103\/1735-5362.293512","article-title":"Synthesis and antileishmanial effect of a few cyclic and non-cyclic n-aryl enamino amide derivatives","volume":"15","author":"Mohammadi-Ghalehbin","year":"2020","journal-title":"Res Pharm Sci"},{"issue":"8","key":"R5-20241215","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/microorganisms8081201","article-title":"Leishmania immunity: advancing immunotherapy and vaccine development","volume":"8","author":"Ikeogu","year":"2020","journal-title":"Microorganisms"},{"issue":"3","key":"R6-20241215","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.vaccine.2012.11.032","article-title":"The potential economic value of a cutaneous leishmaniasis vaccine in seven endemic countries in the Americas","volume":"31","author":"Bacon","year":"2013","journal-title":"Vaccine"},{"issue":"26","key":"R7-20241215","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1016\/j.vaccine.2015.12.071","article-title":"Status of vaccine research and development of vaccines for leishmaniasis","volume":"34","author":"Gillespie","year":"2016","journal-title":"Vaccine"},{"key":"R8-20241215","first-page":"399","article-title":"Leishmania vaccine development: a comprehensive review","author":"Saini","year":"2024","journal-title":"Cell Immunol"},{"issue":"6","key":"R9-20241215","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1021\/acs.chemrev.9b00472","article-title":"Peptide-based vaccines: current progress and future challenges","volume":"120","author":"Malonis","year":"2020","journal-title":"Chem Rev"},{"issue":"3","key":"R10-20241215","doi-asserted-by":"crossref","first-page":"110804","DOI":"10.1016\/j.humimm.2024.110804","article-title":"Multi-epitope vaccines, from design to expression; an in silico approach","volume":"85","author":"Mortazavi","year":"2024","journal-title":"Hum Immunol"},{"issue":"3-4","key":"R11-20241215","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.exppara.2004.03.005","article-title":"Leishmania tropica: cysteine proteases are essential for growth and pathogenicity","volume":"106","author":"Mahmoudzadeh-Niknam","year":"2004","journal-title":"Exp Parasitol"},{"key":"R12-20241215","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1471-2199-6-3","article-title":"Role of Leishmania (Leishmania) chagasi amastigote cysteine protease in intracellular parasite survival: studies by gene disruption and antisense mRNA inhibition","volume":"6","author":"Mundodi","year":"2005","journal-title":"BMC Mol Biol"},{"key":"R13-20241215","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3389\/fimmu.2015.00524","article-title":"Kinetoplastid membrane protein-11 as a vaccine candidate and a virulence factor in Leishmania","volume":"6","author":"De Mendonca","year":"2015","journal-title":"Front Immunol"},{"issue":"7","key":"R14-20241215","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1007\/s00436-018-5915-6","article-title":"A lentiviral vaccine expressing KMP11-HASPB fusion protein increases immune response to Leishmania major in BALB\/C","volume":"117","author":"Mortazavidehkordi","year":"2018","journal-title":"Parasitol Res"},{"issue":"7","key":"R15-20241215","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1016\/j.ymthe.2021.03.020","article-title":"Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan","volume":"29","author":"Younis","year":"2021","journal-title":"Mol Ther"},{"issue":"12","key":"R16-20241215","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.2174\/0929867324666170113112759","article-title":"Fc-fusion proteins in therapy: an updated view","volume":"24","author":"Jafari","year":"2017","journal-title":"Curr Med Chem"},{"issue":"6","key":"R17-20241215","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.copbio.2011.06.012","article-title":"Strategies for extended serum half-life of protein therapeutics","volume":"22","author":"Kontermann","year":"2011","journal-title":"Curr Opin Biotechnol"},{"issue":"45","key":"R18-20241215","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.1016\/j.vaccine.2021.09.077","article-title":"Development of an IgG-Fc fusion COVID-19 subunit vaccine, AKS\u2013452","volume":"39","author":"Alleva","year":"2021","journal-title":"Vaccine"},{"issue":"9","key":"R19-20241215","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.vaccine.2022.01.043","article-title":"Phase I interim results of a phase I\/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS\u2013452","volume":"40","author":"Janssen","year":"2022","journal-title":"Vaccine"},{"key":"R20-20241215","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-2105-8-4","article-title":"VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines","volume":"8","author":"Doytchinova","year":"2007","journal-title":"BMC Bioinformatics"},{"issue":"W1","key":"R21-20241215","doi-asserted-by":"crossref","first-page":"W525","DOI":"10.1093\/nar\/gks438","article-title":"Immune epitope database analysis resource","volume":"40","author":"Kim","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"R22-20241215","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1745-6150-8-30","article-title":"Designing of interferon-gamma inducing MHC class-II binders","volume":"8","author":"Dhanda","year":"2013","journal-title":"Biol Direct"},{"issue":"1","key":"R23-20241215","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/prot.21078","article-title":"Prediction of continuous B-cell epitopes in an antigen using recurrent neural network","volume":"65","author":"Saha","year":"2006","journal-title":"Proteins"},{"issue":"W1","key":"R24-20241215","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"},{"issue":"6","key":"R25-20241215","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1093\/bioinformatics\/btt619","article-title":"AllergenFP: allergenicity prediction by descriptor fingerprints","volume":"30","author":"Dimitrov","year":"2014","journal-title":"Bioinformatics"},{"issue":"9","key":"R26-20241215","doi-asserted-by":"crossref","first-page":"e73957","DOI":"10.1371\/journal.pone.0073957","article-title":"In silico approach for predicting toxicity of peptides and proteins","volume":"8","author":"Gupta","year":"2013","journal-title":"PLoS One"},{"issue":"23","key":"R27-20241215","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1093\/bioinformatics\/btq551","article-title":"High-throughput prediction of protein antigenicity using protein microarray data","volume":"26","author":"Magnan","year":"2010","journal-title":"Bioinformatics"},{"issue":"17","key":"R28-20241215","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/bioinformatics\/btp386","article-title":"SOLpro: accurate sequence-based prediction of protein solubility","volume":"25","author":"Magnan","year":"2009","journal-title":"Bioinformatics"},{"key":"R29-20241215","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1471-2105-9-40","article-title":"I-TASSER server for protein 3D structure prediction","volume":"9","author":"Zhang","year":"2008","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"R30-20241215","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/0471250953.bi0508s52","article-title":"Protein structure and function prediction using I-TASSER","volume":"52","author":"Yang","year":"2015","journal-title":"Curr Protoc Bioinformatics"},{"issue":"Web Server issue","key":"R31-20241215","doi-asserted-by":"crossref","first-page":"W384","DOI":"10.1093\/nar\/gkt458","article-title":"GalaxyRefine: protein structure refinement driven by side-chain repacking","volume":"41","author":"Heo","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"R32-20241215","doi-asserted-by":"crossref","first-page":"930257","DOI":"10.1155\/2012\/930257","article-title":"Toll-like receptors in leishmania infections: guardians or promoters?","volume":"2012","author":"Faria","year":"2012","journal-title":"J Parasitol Res"},{"issue":"Web Server issue","key":"R33-20241215","doi-asserted-by":"crossref","first-page":"W271","DOI":"10.1093\/nar\/gku339","article-title":"iMODS: internal coordinates normal mode analysis server","volume":"42","author":"Lopez-Blanco","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"R34-20241215","doi-asserted-by":"crossref","first-page":"e9862","DOI":"10.1371\/journal.pone.0009862","article-title":"Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system","volume":"5","author":"Rapin","year":"2010","journal-title":"PLoS One"},{"key":"R35-20241215","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/842329","article-title":"How the interval between prime and boost injection affects the immune response in a computational model of the immune system","volume":"2012","author":"Castiglione","year":"2012","journal-title":"Comput Math Methods Med"},{"issue":"3","key":"R36-20241215","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1021\/acs.chemrev.8b00290","article-title":"Utility of B-factors in protein science: interpreting rigidity, flexibility, and internal motion and engineering thermostability","volume":"119","author":"Sun","year":"2019","journal-title":"Chem Rev"},{"issue":"4","key":"R37-20241215","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00894-023-05503-w","article-title":"In silico designing of a novel polyvalent multi-subunit peptide vaccine leveraging cross-immunity against human visceral and cutaneous leishmaniasis: an immunoinformatics-based approach","volume":"29","author":"Bhattacharjee","year":"2023","journal-title":"J Mol Model"},{"key":"R38-20241215","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fpubh.2020.00011","article-title":"The geographical distribution of cutaneous leishmaniasis causative agents in Iran and its neighboring countries, a review","volume":"8","author":"Ghatee","year":"2020","journal-title":"Front Public Health"},{"issue":"6","key":"R39-20241215","doi-asserted-by":"crossref","first-page":"623","DOI":"10.4103\/1735-5362.327508","article-title":"Artemether-loaded nanostructured lipid carriers: preparation, characterization, and evaluation of: in vitro: effect on: Leishmania major","volume":"16","author":"Rahnama","year":"2021","journal-title":"Res Pharm Sci"},{"issue":"1","key":"R40-20241215","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s13071-016-1553-y","article-title":"Possibilities and challenges for developing a successful vaccine for leishmaniasis","volume":"9","author":"Srivastava","year":"2016","journal-title":"Parasit Vectors"},{"key":"R41-20241215","first-page":"10","article-title":"Cutaneous leishmaniasis: update on vaccine development","volume":"9","author":"Whyte","year":"2017","journal-title":"Hum Parasit Dis (Auckl)"},{"key":"R42-20241215","first-page":"3","article-title":"The impact of bioinformatics on vaccine design and development","volume":"2","author":"Mar\u00eda","year":"2017","journal-title":"Vaccines"},{"key":"R43-20241215","doi-asserted-by":"crossref","first-page":"2496713","DOI":"10.1155\/2020\/2496713","article-title":"Review on the role of host immune response in protection and immunopathogenesis during cutaneous leishmaniasis infection","volume":"2020","author":"Dubie","year":"2020","journal-title":"J Immunol Res"},{"key":"R44-20241215","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cellimm.2016.07.010","article-title":"Memory T cells in cutaneous leishmaniasis","volume":"309","author":"Glennie","year":"2016","journal-title":"Cell Immunol"},{"key":"R45-20241215","doi-asserted-by":"crossref","first-page":"1063291","DOI":"10.3389\/fcimb.2022.1063291","article-title":"Humoral response in Leishmaniasis","volume":"12","author":"Conde","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"R46-20241215","doi-asserted-by":"crossref","first-page":"9044","DOI":"10.1038\/s41598-018-26689-7","article-title":"Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii","author":"Solanki","year":"2018","journal-title":"Sci Rep"},{"issue":"2","key":"R47-20241215","doi-asserted-by":"crossref","first-page":"e30839","DOI":"10.1371\/journal.pone.0030839","article-title":"Synthetic Toll like receptor-4 (TLR-4) agonist peptides as a novel class of adjuvants","volume":"7","author":"Shanmugam","year":"2012","journal-title":"PloS One"},{"issue":"4","key":"R48-20241215","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1128\/IAI.72.4.1920-1928.2004","article-title":"Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major","volume":"72","author":"Kropf","year":"2004","journal-title":"Infect Immun"},{"issue":"3","key":"R49-20241215","doi-asserted-by":"crossref","first-page":"284","DOI":"10.4103\/1735-5362.343082","article-title":"Design and production of a novel chimeric human growth hormone superagonist fused to human Fc domain","volume":"17","author":"Mirbaha","year":"2022","journal-title":"Res Pharm Sci"},{"issue":"3","key":"R50-20241215","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1128\/IAI.01090-07","article-title":"Toll-like receptors and leishmaniasis","volume":"76","author":"Tuon","year":"2007","journal-title":"Infect Immun"},{"issue":"2","key":"R51-20241215","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3390\/vaccines11020304","article-title":"Immunoinformatics approach to design a multi-epitope nanovaccine against Leishmania parasite: elicitation of cellular immune responses","volume":"11","author":"Margaroni","year":"2023","journal-title":"Vaccines"}],"container-title":["Research in Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/RPS.RPS_145_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:44:45Z","timestamp":1787838285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/RPS.RPS_145_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/rps.rps_145_24","relation":{},"ISSN":["1735-5362","1735-9414"],"issn-type":[{"value":"1735-5362","type":"print"},{"value":"1735-9414","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-08-08","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}