{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:17:14Z","timestamp":1784809034836,"version":"3.55.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Leishmaniasis is a vector-borne disease caused by the protozoan parasite of <jats:italic>Leishmania<\/jats:italic> genus and is a complex disease affecting mostly tropical regions of the world. Unfortunately, despite the extensive effort made, there is no vaccine available for human use. Undoubtedly, a comprehensive understanding of the host-vector-parasite interaction is substantial for developing an effective prophylactic vaccine. Recently the role of sandfly saliva on disease progression has been uncovered which can make a substantial contribution in vaccine design. In this review we try to focus on the strategies that most probably meet the prerequisites of vaccine development (based on the current understandings) including live attenuated\/non-pathogenic and subunit DNA vaccines. Innovative approaches such as reverse genetics, CRISP\/R-Cas9 and antibiotic-free selection are now available to promisingly compensate for intrinsic drawbacks associated with these platforms. Our main goal is to call more attention toward the prerequisites of effective vaccine development while controlling the disease outspread is a substantial need.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1326369","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T05:17:41Z","timestamp":1712121461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Live attenuated-nonpathogenic Leishmania and DNA structures as promising vaccine platforms against leishmaniasis: innovations can make waves"],"prefix":"10.3389","volume":"15","author":[{"given":"Negar","family":"Seyed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahereh","family":"Taheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima","family":"Rafati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.3390\/genes11101159","article-title":"Application of CRISPR\/Cas9-based reverse genetics in Leishmania braziliensis: conserved roles for HSP100 and HSP23","volume":"11","author":"Adaui","year":"2020","journal-title":"Genes (Basel)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.plasmid.2018.12.002","article-title":"The antibiotic resistance-free mammalian expression plasmid vector pPAL for development of third generation vaccines","volume":"101","author":"Alcolea","year":"2019","journal-title":"Plasmid"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1017\/S0031182009005873","article-title":"Searching for virulence factors in the non-pathogenic parasite to humans Leishmania tarentolae","volume":"136","author":"Azizi","year":"2009","journal-title":"Parasitology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"100007","DOI":"10.1016\/j.btecx.2019.100007","article-title":"Small-scale GMP production of plasmid DNA using a simplified and fully disposable production method","volume":"306","author":"Bakker","year":"2019","journal-title":"J. Biotechnol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13071-023-05651-1","article-title":"Leishmania tarentolae: a vaccine platform to target dendritic cells and a surrogate pathogen for next generation vaccine research in leishmaniases and viral infections","volume":"16","author":"Bandi","year":"2023","journal-title":"Parasit. Vectors"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1084\/jem.194.10.1497","article-title":"The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure","volume":"194","author":"Belkaid","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e0004963","DOI":"10.1371\/journal.pntd.0004963","article-title":"Live attenuated Leishmania donovani Centrin Knock out parasites generate non-inferior protective immune response in aged mice against visceral Leishmaniasis","volume":"10","author":"Bhattacharya","year":"2016","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"6372","DOI":"10.1128\/IAI.73.10.6372-6382.2005","article-title":"Live nonpathogenic parasitic vector as a candidate vaccine against visceral leishmaniasis","volume":"73","author":"Breton","year":"2005","journal-title":"Infect. Immun."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18388\/abp.2011_2278","article-title":"Prokaryotic toxin-antitoxin systems--the role in bacterial physiology and application in molecular biology","volume":"58","author":"Bukowski","year":"2011","journal-title":"Acta Biochim. Pol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1159\/000373923","article-title":"Interactions between neutrophils and Leishmania braziliensis amastigotes facilitate cell activation and parasite clearance","volume":"7","author":"Carlsen","year":"2015","journal-title":"J. Innate Immun."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e1008674","DOI":"10.1371\/journal.ppat.1008674","article-title":"The role of dermis resident macrophages and their interaction with neutrophils in the early establishment of Leishmania major infection transmitted by sand fly bite","volume":"16","author":"Chaves","year":"2020","journal-title":"PLoS Pathog."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"e943","DOI":"10.1371\/journal.pntd.0000943","article-title":"Vaccines for the leishmaniases: proposals for a research agenda","volume":"5","author":"Costa","year":"2011","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"26e","DOI":"10.1093\/nar\/29.5.e26","article-title":"Escherichia coli strains that allow antibiotic-free plasmid selection and maintenance by repressor titration","volume":"29","author":"Cranenburgh","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e0004205","DOI":"10.1371\/journal.pntd.0004205","article-title":"Depletion of UDP-glucose and UDP-galactose using a Degron system leads to growth cessation of Leishmania major","volume":"9","author":"Damerow","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/sj.gt.3300540","article-title":"A new DNA vehicle for nonviral gene delivery: supercoiled minicircle","volume":"4","author":"Darquet","year":"1997","journal-title":"Gene Ther."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e0007939","DOI":"10.1371\/journal.pntd.0007939","article-title":"Lactococcus lactis expressing sand fly PpSP15 salivary protein confers long-term protection against Leishmania major in BALB\/c mice","volume":"14","author":"Davarpanah","year":"2020","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e1005296","DOI":"10.1371\/journal.ppat.1005296","article-title":"Amastin knockdown in Leishmania braziliensis affects parasite-macrophage interaction and results in impaired viability of intracellular amastigotes","volume":"11","author":"de Paiva","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e13815","DOI":"10.1371\/journal.pone.0013815","article-title":"Neutrophils reduce the parasite burden in Leishmania (Leishmania) amazonensis-infected macrophages","volume":"5","author":"de Souza Carmo","year":"2010","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"140197","DOI":"10.1098\/rsob.140197","article-title":"A toolkit enabling efficient, scalable and reproducible gene tagging in trypanosomatids","volume":"5","author":"Dean","year":"2015","journal-title":"Open Biol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.chom.2017.12.002","article-title":"Gut microbes egested during bites of infected sand flies augment severity of Leishmaniasis via Inflammasome-derived IL-1beta","volume":"23","author":"Dey","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1038\/mt.2013.85","article-title":"Minicircle DNA is superior to plasmid DNA in eliciting antigen-specific CD8+ T-cell responses","volume":"21","author":"Dietz","year":"2013","journal-title":"Mol. Ther."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3347\/kjp.2022.60.6.379","article-title":"Leishmania vaccines: the current situation with its promising aspect for the future","volume":"60","author":"Dinc","year":"2022","journal-title":"Korean J. Parasitol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3389\/fcimb.2019.00100","article-title":"Modulation of host-pathogen communication by extracellular vesicles (EVs) of the protozoan parasite Leishmania","volume":"9","author":"Dong","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.molimm.2021.04.003","article-title":"Extracellular vesicles and leishmaniasis: current knowledge and promising avenues for future development","volume":"135","author":"Dong","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.molbiopara.2017.06.005","article-title":"Recent advances in Leishmania reverse genetics: manipulating a manipulative parasite","volume":"216","author":"Duncan","year":"2017","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1016\/j.drudis.2021.06.008","article-title":"Methods to improve the immunogenicity of plasmid DNA vaccines","volume":"26","author":"Eusebio","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.coi.2020.01.006","article-title":"DNA vaccines: prime time is now","volume":"65","author":"Gary","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref28","doi-asserted-by":"publisher","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":"ref29","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1084\/jem.20142101","article-title":"Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection","volume":"212","author":"Glennie","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/1472-6750-8-61","article-title":"Plasmid selection in Escherichia coli using an endogenous essential gene marker","volume":"8","author":"Goh","year":"2008","journal-title":"BMC Biotechnol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e1610","DOI":"10.1371\/journal.pntd.0001610","article-title":"KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi","volume":"6","author":"Gomes","year":"2012","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/mt.2012.244","article-title":"Minicircle DNA vectors achieve sustained expression reflected by active chromatin and transcriptional level","volume":"21","author":"Gracey Maniar","year":"2013","journal-title":"Mol. Ther."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3390\/v12020168","article-title":"The first non-LRV RNA virus in Leishmania","volume":"12","author":"Grybchuk","year":"2020","journal-title":"Viruses"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1038\/s41467-021-23002-5","article-title":"A sand fly salivary protein acts as a neutrophil chemoattractant","volume":"12","author":"Guimaraes-Costa","year":"2021","journal-title":"Nat. Commun."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1084\/jem.186.7.1137","article-title":"Vaccination with DNA encoding the immunodominant LACK parasite antigen confers protective immunity to mice infected with Leishmania major","volume":"186","author":"Gurunathan","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/S0952-7915(00)00118-7","article-title":"DNA vaccines: a key for inducing long-term cellular immunity","volume":"12","author":"Gurunathan","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"106298","DOI":"10.1016\/j.actatropica.2021.106298","article-title":"A candidate vaccine composed of live nonpathogenic Iranian lizard Leishmania mixed with chitin microparticles protects mice against Leishmania major infection","volume":"227","author":"Haghdoust","year":"2022","journal-title":"Acta Trop."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3389\/fcimb.2012.00099","article-title":"Leishmania RNA virus: when the host pays the toll","volume":"2","author":"Hartley","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e2001812","DOI":"10.1002\/adhm.202001812","article-title":"Next-generation vaccines: nanoparticle-mediated DNA and mRNA delivery","volume":"10","author":"Ho","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"16.29","DOI":"10.4049\/jimmunol.206.Supp.16.29","article-title":"Effector function prior to establishment of the phagosomal pathogen niche is required for protective CD4+ T cell-mediated immunity against Leishmania","volume":"206","author":"Hohman","year":"2021","journal-title":"J. Immunol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e1009944","DOI":"10.1371\/journal.ppat.1009944","article-title":"Protective CD4+ Th1 cell-mediated immunity is reliant upon execution of effector function prior to the establishment of the pathogen niche","volume":"17","author":"Hohman","year":"2021","journal-title":"PLoS Pathog."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.pt.2019.04.002","article-title":"CD4(+) T cell-mediated immunity against the Phagosomal pathogen Leishmania: implications for vaccination","volume":"35","author":"Hohman","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14411\/fp.2016.016","article-title":"T7 polymerase-driven transcription is downregulated in metacyclic promastigotes and amastigotes of Leishmania mexicana","volume":"63","author":"Ishemgulova","year":"2016","journal-title":"Folia Parasitol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"864031","DOI":"10.3389\/fimmu.2022.864031","article-title":"Leishmania major Centrin gene-deleted parasites generate skin resident memory T-cell immune response analogous to Leishmanization","volume":"13","author":"Ismail","year":"2022","journal-title":"Front. Immunol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e00407-19","DOI":"10.1128\/AEM.00407-19","article-title":"A novel Cre recombinase-mediated in vivo Minicircle DNA (CRIM) vaccine provides partial protection against Newcastle disease virus","volume":"85","author":"Jiang","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref46","first-page":"96","volume-title":"Role of sand fly saliva on Leishmania-infection and the potential of vector salivary proteins as vaccines. Skin and arthropod vectors","author":"Kamhavi","year":"2018"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1016\/S1286-4579(00)01331-9","article-title":"The biological and immunomodulatory properties of sand fly saliva and its role in the establishment of Leishmania infections","volume":"2","author":"Kamhawi","year":"2000","journal-title":"Microbes Infect."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41541-022-00574-x","article-title":"Centrin-deficient Leishmania mexicana confers protection against Old World visceral leishmaniasis","volume":"7","author":"Karmakar","year":"2022","journal-title":"NPJ Vaccines."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.molimm.2015.08.001","article-title":"Leishmania tarentolae secreting the sand fly salivary antigen PpSP15 confers protection against Leishmania major infection in a susceptible BALB\/c mice model","volume":"67","author":"Katebi","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1080\/14760584.2021.1990043","article-title":"Overcoming roadblocks in the development of vaccines for leishmaniasis","volume":"20","author":"Kaye","year":"2021","journal-title":"Expert Rev. Vaccines"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.3389\/fimmu.2020.01725","article-title":"Evaluation of Leishmanization using Iranian lizard Leishmania mixed with CpG-ODN as a candidate vaccine against experimental murine Leishmaniasis","volume":"11","author":"Keshavarzian","year":"2020","journal-title":"Front. Immunol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/nrg2432","article-title":"DNA vaccines: ready for prime time?","volume":"9","author":"Kutzler","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"895234","DOI":"10.3389\/fimmu.2022.895234","article-title":"Leishmania tarentolae as potential live vaccine co-expressing distinct salivary gland proteins against experimental cutaneous leishmaniasis in BALB\/c mice model","volume":"13","author":"Lajevardi","year":"2022","journal-title":"Front. Immunol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.actbio.2018.08.033","article-title":"Engineering DNA vaccines against infectious diseases","volume":"80","author":"Lee","year":"2018","journal-title":"Acta Biomater."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"e0005600","DOI":"10.1371\/journal.pntd.0005600","article-title":"Insights into the sand fly saliva: blood-feeding and immune interactions between sand flies, hosts, and Leishmania","volume":"11","author":"Lestinova","year":"2017","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"36483","DOI":"10.1038\/srep36483","article-title":"Minicircle HBV cccDNA with a Gaussia luciferase reporter for investigating HBV cccDNA biology and developing cccDNA-targeting drugs","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1586\/14760584.2016.1124762","article-title":"Molecular mechanisms for enhanced DNA vaccine immunogenicity","volume":"15","author":"Li","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/pharmaceutics12010030","article-title":"Engineered Nanodelivery systems to improve DNA vaccine technologies","volume":"12","author":"Lim","year":"2020","journal-title":"Pharmaceutics"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/j.1600-065X.2010.00980.x","article-title":"DNA vaccines: an historical perspective and view to the future","volume":"239","author":"Liu","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s13046-019-1154-7","article-title":"Cancer DNA vaccines: current preclinical and clinical developments and future perspectives","volume":"38","author":"Lopes","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"e00227-19","DOI":"10.1128\/IAI.00227-19","article-title":"Intradermal synthetic DNA vaccination generates Leishmania-specific T cells in the skin and protection against Leishmania major","volume":"87","author":"Louis","year":"2019","journal-title":"Infect. Immun."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1038\/mt.2012.65","article-title":"The extragenic spacer length between the 5\u2032 and 3\u2032 ends of the transgene expression cassette affects transgene silencing from plasmid-based vectors","volume":"20","author":"Lu","year":"2012","journal-title":"Mol. Ther."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1074\/jbc.275.3.1625","article-title":"Size-dependent DNA mobility in cytoplasm and nucleus","volume":"275","author":"Lukacs","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"6454","DOI":"10.1016\/j.vaccine.2009.06.017","article-title":"Improved antibiotic-free DNA vaccine vectors utilizing a novel RNA based plasmid selection system","volume":"27","author":"Luke","year":"2009","journal-title":"Vaccine"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"11965","DOI":"10.1073\/pnas.1004599107","article-title":"Expansion of the target of rapamycin (TOR) kinase family and function in Leishmania shows that TOR3 is required for acidocalcisome biogenesis and animal infectivity","volume":"107","author":"Madeira da Silva","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jbiotec.2010.01.025","article-title":"Marker-free plasmids for gene therapeutic applications--lack of antibiotic resistance gene substantially improves the manufacturing process","volume":"146","author":"Mairhofer","year":"2010","journal-title":"J. Biotechnol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/npre.2008.2395.1","article-title":"pFAR plasmids: new eukaryotic expression vectors for gene therapy, devoid of antibiotic resistance markers","author":"Marie","year":"2008","journal-title":"Nat. Preced."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/jgm.1441","article-title":"pFARs, plasmids free of antibiotic resistance markers, display high-level transgene expression in muscle, skin and tumour cells","volume":"12","author":"Marie","year":"2010","journal-title":"J. Gene Med."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1080\/14789450.2020.1812390","article-title":"Transcriptomic profiling in cutaneous Leishmaniasis patients","volume":"17","author":"Masoudzadeh","year":"","journal-title":"Expert Rev. Proteomics"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"16198","DOI":"10.1038\/s41598-020-72671-7","article-title":"Molecular signatures of anthroponotic cutaneous leishmaniasis in the lesions of patients infected with Leishmania tropica","volume":"10","author":"Masoudzadeh","year":"","journal-title":"Sci. Rep."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"e0003588","DOI":"10.1371\/journal.pntd.0003588","article-title":"Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase","volume":"9","author":"McCall","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s002810000014","article-title":"The role of CpG in DNA vaccines","volume":"22","author":"McCluskie","year":"2000","journal-title":"Springer Semin. Immunopathol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"5122","DOI":"10.4049\/jimmunol.166.8.5122","article-title":"The potency and durability of DNA-and protein-based vaccines against Leishmania major evaluated using low-dose, intradermal challenge","volume":"166","author":"Mendez","year":"2001","journal-title":"J. Immunol."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13071-021-04973-2","article-title":"Detection of Leishmania tarentolae in lizards, sand flies and dogs in southern Italy, where Leishmania infantum is endemic: hindrances and opportunities","volume":"14","author":"Mendoza-Roldan","year":"2021","journal-title":"Parasit. Vectors"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"e1326","DOI":"10.1111\/tbed.14660","article-title":"Leishmania tarentolae: a new frontier in the epidemiology and control of the leishmaniases","volume":"69","author":"Mendoza-Roldan","year":"2022","journal-title":"Transbound. Emerg. Dis."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.3390\/microorganisms11041043","article-title":"Next-generation Leishmanization: revisiting molecular targets for selecting genetically engineered live-attenuated Leishmania","volume":"11","author":"Moreira","year":"2023","journal-title":"Microorganisms."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"23125","DOI":"10.1038\/srep23125","article-title":"Minicircle DNA provides enhanced and prolonged transgene expression following airway gene transfer","volume":"6","author":"Munye","year":"2016","journal-title":"Sci. Rep."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1099\/vir.0.19701-0","article-title":"A human immunodeficiency virus 1 (HIV-1) clade a vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans","volume":"85","author":"Mwau","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"e13018","DOI":"10.1111\/pim.13018","article-title":"Comparison of the long-term and short-term protection in mouse model of Leishmania major infection following vaccination with live Iranian lizard Leishmania mixed with chitin microparticles","volume":"46","author":"Noroozbeygi","year":"2023","journal-title":"Parasite Immunol."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s42690-020-00184-x","article-title":"Bacteria composition and diversity in the gut of sand fly: impact on Leishmania and sand fly development","volume":"41","author":"Omondi","year":"2021","journal-title":"Int. J. Trop. Insect. Sci."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"639801","DOI":"10.3389\/fcimb.2021.639801","article-title":"Revival of Leishmanization and Leishmanin","volume":"11","author":"Pacheco-Fernandez","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"e12732","DOI":"10.1111\/pim.12732","article-title":"Genetically modified live attenuated vaccine: a potential strategy to combat visceral leishmaniasis","volume":"42","author":"Pandey","year":"2020","journal-title":"Parasite Immunol."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1089\/hum.2016.122","article-title":"Treatment of human B-cell lymphomas using Minicircle DNA vector expressing anti-CD3\/CD20 in a mouse model","volume":"28","author":"Pang","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"649348","DOI":"10.3389\/fimmu.2021.649348","article-title":"The impact of neutrophil recruitment to the skin on the pathology induced by Leishmania infection","volume":"12","author":"Passelli","year":"2021","journal-title":"Front. Immunol."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"4832","DOI":"10.4049\/jimmunol.1201676","article-title":"Evaluation of recombinant Leishmania polyprotein plus glucopyranosyl lipid a stable emulsion vaccines against sand fly-transmitted Leishmania major in C57BL\/6 mice","volume":"189","author":"Peters","year":"2012","journal-title":"J. Immunol."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1126\/science.1159194","article-title":"In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies","volume":"321","author":"Peters","year":"2008","journal-title":"Science"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"e1000484","DOI":"10.1371\/journal.ppat.1000484","article-title":"Vector transmission of leishmania abrogates vaccine-induced protective immunity","volume":"5","author":"Peters","year":"2009","journal-title":"PLoS Pathog."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e1004538","DOI":"10.1371\/journal.ppat.1004538","article-title":"Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection","volume":"10","author":"Peters","year":"2014","journal-title":"PLoS Pathog."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1111\/j.1462-5822.2009.01348.x","article-title":"The impact of vector-mediated neutrophil recruitment on cutaneous leishmaniasis","volume":"11","author":"Peters","year":"2009","journal-title":"Cell. Microbiol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/biot.200600017","article-title":"Using ColE1-derived RNA I for suppression of a bacterially encoded gene: implication for a novel plasmid addiction system","volume":"1","author":"Pfaffenzeller","year":"2006","journal-title":"Biotechnol. J."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"12283","DOI":"10.1073\/pnas.1400472111","article-title":"History of vaccination","volume":"111","author":"Plotkin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"6695","DOI":"10.1016\/j.vaccine.2009.08.091","article-title":"Antibiotic resistance free plasmid DNA expressing LACK protein leads towards a protective Th1 response against Leishmania infantum infection","volume":"27","author":"Ramos","year":"2009","journal-title":"Vaccine"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1093\/nar\/gkr834","article-title":"Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species","volume":"40","author":"Raymond","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1016\/j.jid.2018.12.012","article-title":"TLR2 signaling in skin nonhematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection","volume":"139","author":"Ronet","year":"2019","journal-title":"J. Invest. Dermatol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/mt.2010.303","article-title":"The actin cytoskeleton has an active role in the electrotransfer of plasmid DNA in mammalian cells","volume":"19","author":"Rosazza","year":"2011","journal-title":"Mol. Ther."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.mib.2018.07.005","article-title":"The criminal association of Leishmania parasites and viruses","volume":"46","author":"Rossi","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/bit.20327","article-title":"Characterization of the metabolic burden on Escherichia coli DH1 cells imposed by the presence of a plasmid containing a gene therapy sequence","volume":"88","author":"Rozkov","year":"2004","journal-title":"Biotechnol. Bioeng."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/ni.2853","article-title":"Vaccines against tropical parasitic diseases: a persisting answer to a persisting problem","volume":"15","author":"Sacks","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref100","volume-title":"Leishmaniasis transmission biology: Role of promastigote secretory gel as a transmission determinant","author":"Sainz","year":"2014"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"R27","DOI":"10.1016\/j.cub.2003.12.019","article-title":"Centrosomes: Sfi1p and centrin unravel a structural riddle","volume":"14","author":"Salisbury","year":"2004","journal-title":"Curr. Biol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"e2174","DOI":"10.1371\/journal.pntd.0002174","article-title":"Development of novel prime-boost strategies based on a tri-gene fusion recombinant L. tarentolae vaccine against experimental murine visceral leishmaniasis","volume":"7","author":"Saljoughian","year":"2013","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1016\/j.vaccine.2009.01.043","article-title":"Intradermal hepatitis B vaccination: a systematic review and meta-analysis","volume":"27","author":"Sangare","year":"2009","journal-title":"Vaccine"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.molbiopara.2017.06.006","article-title":"A DiCre recombinase-based system for inducible expression in Leishmania major","volume":"216","author":"Santos","year":"2017","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"13627","DOI":"10.1038\/srep13627","article-title":"Photo-activatable Cre recombinase regulates gene expression in vivo","volume":"5","author":"Schindler","year":"2015","journal-title":"Sci. Rep."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"a038059","DOI":"10.1101\/cshperspect.a038059","article-title":"Long-lived skin-resident memory T cells contribute to concomitant immunity in cutaneous Leishmaniasis","volume":"12","author":"Scott","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"25703","DOI":"10.1074\/jbc.M402794200","article-title":"Centrin gene disruption impairs stage-specific basal body duplication and cell cycle progression in Leishmania","volume":"279","author":"Selvapandiyan","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"43253","DOI":"10.1074\/jbc.M106806200","article-title":"Expression of a mutant form of Leishmania donovani centrin reduces the growth of the parasite","volume":"276","author":"Selvapandiyan","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.pt.2021.07.003","article-title":"Leishmaniasis: the act of transmission","volume":"37","author":"Serafim","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.3389\/fimmu.2018.01227","article-title":"Translating observations from Leishmanization into non-living vaccines: the potential of dendritic cell-based vaccination strategies against Leishmania","volume":"9","author":"Seyed","year":"2018","journal-title":"Front. Immunol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"155247","DOI":"10.1016\/j.cyto.2020.155247","article-title":"Th1 concomitant immune response mediated by IFN-gamma protects against sand fly delivered Leishmania infection: implications for vaccine design","volume":"147","author":"Seyed","year":"2021","journal-title":"Cytokine"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00005-008-0010-9","article-title":"Live attenuated Leishmania vaccines: a potential strategic alternative","volume":"56","author":"Silvestre","year":"2008","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"12","DOI":"10.46439\/immunol.1.004","article-title":"Vaccine for leishmaniasis: new era of CRISPR generated live attenuated dermotropic Leishmania","volume":"1","author":"Singh","year":"2022","journal-title":"J Cell Mol Immunol."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1126\/science.1087499","article-title":"Persistence without pathology in phosphoglycan-deficient Leishmania major","volume":"301","author":"Spath","year":"2003","journal-title":"Science"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"3622","DOI":"10.1128\/IAI.72.6.3622-3627.2004","article-title":"Identification of a compensatory mutant (lpg2-REV) of Leishmania major able to survive as amastigotes within macrophages without LPG2-dependent glycoconjugates and its significance to virulence and immunization strategies","volume":"72","author":"Spath","year":"2004","journal-title":"Infect. Immun."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.omtm.2020.04.009","article-title":"Nanoplasmid vectors co-expressing innate immune agonists enhance DNA vaccines for Venezuelan equine encephalitis virus and Ebola virus","volume":"17","author":"Suschak","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"2837","DOI":"10.1080\/21645515.2017.1330236","article-title":"Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity","volume":"13","author":"Suschak","year":"2017","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.3390\/microorganisms11051322","article-title":"Immunisation with transgenic L. tarentolae expressing gamma glutamyl cysteine synthetase from pathogenic leishmania species protected against L. major and L. donovani infection in a murine model","volume":"11","author":"Topuz Ata","year":"2023","journal-title":"Microorganisms."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.4049\/jimmunol.172.6.3793","article-title":"Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response","volume":"172","author":"Uzonna","year":"2004","journal-title":"J. Immunol."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1084\/jem.194.3.331","article-title":"Toward a defined anti-Leishmania vaccine targeting vector antigens: characterization of a protective salivary protein","volume":"194","author":"Valenzuela","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1038\/mt.2011.182","article-title":"New generation of plasmid backbones devoid of antibiotic resistance marker for gene therapy trials","volume":"19","author":"Vandermeulen","year":"2011","journal-title":"Mol. Ther."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3390\/pathogens11040431","article-title":"The history of live attenuated Centrin gene-deleted Leishmania vaccine candidates","volume":"11","author":"Volpedo","year":"2022","journal-title":"Pathogens"},{"key":"ref123","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1080\/14760584.2021.1969231","article-title":"From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection","volume":"20","author":"Volpedo","year":"2021","journal-title":"Expert Rev. Vaccines"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1128\/JVI.02757-13","article-title":"In vivo electroporation of minicircle DNA as a novel method of vaccine delivery to enhance HIV-1-specific immune responses","volume":"88","author":"Wang","year":"2014","journal-title":"J. Virol."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3390\/vaccines1030225","article-title":"Vector design for improved DNA vaccine efficacy","volume":"1","author":"Williams","year":"2013","journal-title":"Safety Product. Vaccines (Basel)"},{"key":"ref127","doi-asserted-by":"publisher","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":"ref128","doi-asserted-by":"publisher","first-page":"107849","DOI":"10.1016\/j.exppara.2020.107849","article-title":"The potential of live attenuated vaccines against cutaneous Leishmaniasis","volume":"210","author":"Zabala-Penafiel","year":"2020","journal-title":"Exp. Parasitol."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"3461","DOI":"10.1038\/s41467-020-17154-z","article-title":"A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"e00340-16","DOI":"10.1128\/mSphere.00340-16","article-title":"Optimized CRISPR-Cas9 genome editing for Leishmania and its use to target a multigene family, induce chromosomal translocation, and study DNA break repair mechanisms","volume":"2","author":"Zhang","year":"2017","journal-title":"mSphere"},{"key":"ref131","doi-asserted-by":"publisher","first-page":"e00861","DOI":"10.1128\/mBio.00861-15","article-title":"CRISPR-Cas9-mediated genome editing in Leishmania donovani","volume":"6","author":"Zhang","year":"2015","journal-title":"MBio"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1326369\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T05:17:45Z","timestamp":1712121465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1326369\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":129,"alternative-id":["10.3389\/fmicb.2024.1326369"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1326369","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]},"article-number":"1326369"}}