{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T04:35:10Z","timestamp":1769747710079,"version":"3.49.0"},"reference-count":72,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EPAnEK Operational Programme (NSFR 2014-2020) co-financed by Greece and the European Union (T1EDK-03902)","award":["T1EDK-03902"],"award-info":[{"award-number":["T1EDK-03902"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Control of the intracellular parasite Leishmania (L.) requires the activation of strong type 1 cellular immune responses. Towards this goal, in the present study, a multiepitope chimeric protein named LiChimera was encapsulated into cationic liposomes and its protective efficacy against experimental visceral leishmaniasis was investigated. Liposomal LiChimera conferred significant protection against L. infantum as evidenced by the significantly reduced parasite loads in the spleen and liver. Protection detected in Lipo:LiChimera-immunized mice was dependent on the differentiation of long-lasting cellular immune responses and particularly the induction of antigen-specific multifunctional memory CD4+ TH1 and CD8+ T cells that persisted during infection, as evidenced by the persistent high production of IFN-\u03b3 and IL-2 and proliferation activity. Notably, protected mice were also characterized by significantly low numbers of non-regulatory CD4+ T cells able to co-produce IFN-\u03b3 and IL-10, an important population for disease establishment, as compared to non-immunized control group. Collectively, these results demonstrate that cationic liposomes containing LiChimera can be considered an effective candidate vaccine against visceral leishmaniasis.<\/jats:p>","DOI":"10.3390\/vaccines11081384","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:33:11Z","timestamp":1692581591000},"page":"1384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intramuscular Immunization with a Liposomal Multi-Epitope Chimeric Protein Induces Strong Cellular Immune Responses against Visceral Leishmaniasis"],"prefix":"10.3390","volume":"11","author":[{"given":"Maria","family":"Agallou","sequence":"first","affiliation":[{"name":"Immunology of Infection Group, Department of Microbiology, Hellenic Pasteur Institute, 115 21 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-9547","authenticated-orcid":false,"given":"Maritsa","family":"Margaroni","sequence":"additional","affiliation":[{"name":"Immunology of Infection Group, Department of Microbiology, Hellenic Pasteur Institute, 115 21 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evdokia","family":"Karagouni","sequence":"additional","affiliation":[{"name":"Immunology of Infection Group, Department of Microbiology, Hellenic Pasteur Institute, 115 21 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s40475-021-00232-7","article-title":"A Review of Leishmaniasis: Current Knowledge and Future Directions","volume":"8","author":"Mann","year":"2021","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8965","DOI":"10.1007\/s00253-020-10856-w","article-title":"Recent advances and new strategies on leishmaniasis treatment","volume":"104","author":"Roatt","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ijpara.2020.01.001","article-title":"Vaccination against canine leishmaniasis in Brazil","volume":"50","author":"Nogueira","year":"2020","journal-title":"Int. J. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1016\/j.vaccine.2018.02.111","article-title":"A large-scale field randomized trial demonstrates safety and efficacy of the vaccine LetiFend(R) against canine leishmaniosis","volume":"36","author":"Iniesta","year":"2018","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.1016\/j.vaccine.2005.02.015","article-title":"Leishmanization: Use of an old method for evaluation of candidate vaccines against leishmaniasis","volume":"23","author":"Khamesipour","year":"2005","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1172\/JCI113969","article-title":"Antigen-Specific Immunosuppression in Visceral Leishmaniasis Is Cell-Mediated","volume":"83","author":"Carvalho","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1006\/cyto.2000.0694","article-title":"IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis","volume":"12","author":"Bacellar","year":"2000","journal-title":"Cytokine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"624009","DOI":"10.3389\/fcimb.2021.624009","article-title":"Role of Cytokines in Experimental and Human Visceral Leishmaniasis","volume":"11","author":"Samant","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","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":"ref_10","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrmicro2608","article-title":"Leishmaniasis: Complexity at the host-pathogen interface","volume":"9","author":"Kaye","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/infdis\/jir842","article-title":"Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis","volume":"205","author":"Maroof","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111671","DOI":"10.1016\/j.biopha.2021.111671","article-title":"Host immune response against leishmaniasis and parasite persistence strategies: A review and assessment of recent research","volume":"139","author":"Elmahallawy","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.3389\/fimmu.2018.01043","article-title":"Peptide Vaccines for Leishmaniasis","volume":"9","author":"Cardoso","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3389\/fimmu.2014.00268","article-title":"Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins","volume":"5","author":"Agallou","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"684","DOI":"10.3389\/fimmu.2017.00684","article-title":"A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNgamma-Producing CD8(+) T Cells Essential for the Protection against Experimental Visceral Leishmaniasis","volume":"8","author":"Athanasiou","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_16","first-page":"100","article-title":"A Chimera Containing CD4+ and CD8+ T-Cell Epitopes of the Leishmania donovani Nucleoside Hydrolase (NH36) Optimizes Cross-Protection against Leishmania amazonesis Infection","volume":"8","author":"Nico","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12359","DOI":"10.1111\/pim.12359","article-title":"A recombinant chimeric protein composed of human and mice-specific CD4(+) and CD8(+) T-cell epitopes protects against visceral leishmaniasis","volume":"39","author":"Martins","year":"2017","journal-title":"Parasite Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41541-020-00224-0","article-title":"A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection","volume":"5","author":"Lage","year":"2020","journal-title":"NPJ Vaccines"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.vaccine.2012.11.068","article-title":"Micro\/nanoparticle adjuvants for antileishmanial vaccines: Present and future trends","volume":"31","author":"Badiee","year":"2013","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/2051013617741578","article-title":"Liposomal adjuvant development for leishmaniasis vaccines","volume":"5","author":"Askarizadeh","year":"2017","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1128\/IAI.72.3.1608-1617.2004","article-title":"Combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and synthetic mycobacterial cord factor as an efficient adjuvant for tuberculosis subunit vaccines","volume":"72","author":"Doherty","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1128\/IAI.68.2.791-795.2000","article-title":"ESAT-6 subunit vaccination against Mycobacterium tuberculosis","volume":"68","author":"Brandt","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.actbio.2016.04.012","article-title":"Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus","volume":"41","author":"Ghaffar","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1021\/acs.molpharmaceut.1c00852","article-title":"Assessing the In Vivo Effectiveness of Cationic Lipid Nanoparticles with a Triple Adjuvant for Intranasal Vaccination against the Respiratory Pathogen Bordetella pertussis","volume":"19","author":"Aibani","year":"2022","journal-title":"Mol. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Firdaus, F.Z., Bartlett, S., Hussein, W.M., Lu, L., Wright, Q., Huang, W., Nahar, U.J., Yang, J., Khongkow, M., and Veitch, M. (2023). Liposomal Formulations of a Polyleucine-Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020602"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1586\/erv.10.155","article-title":"One does not fit all: New adjuvants are needed and vaccine formulation is critical","volume":"10","author":"Korsholm","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/2051013614541440","article-title":"Liposomes as vaccine delivery systems: A review of the recent advances","volume":"2","author":"Schwendener","year":"2014","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27206","DOI":"10.1038\/srep27206","article-title":"A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8(+) T Cells","volume":"6","author":"Maji","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8771","DOI":"10.1016\/j.vaccine.2007.10.028","article-title":"Non-coding pDNA bearing immunostimulatory sequences co-entrapped with leishmanial antigens in cationic liposomes elicits almost complete protection against experimental visceral leishmaniasis in BALB\/c mice","volume":"25","author":"Mazumder","year":"2007","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.1016\/j.vaccine.2007.05.042","article-title":"Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response","volume":"25","author":"Bhowmick","year":"2007","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1128\/IAI.00611-07","article-title":"gp63 in stable cationic liposomes confers sustained vaccine immunity to susceptible BALB\/c mice infected with Leishmania donovani","volume":"76","author":"Bhowmick","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fimmu.2018.00018","article-title":"Liposomal Elongation Factor-1alpha Triggers Effector CD4 and CD8 T Cells for Induction of Long-Lasting Protective Immunity against Visceral Leishmaniasis","volume":"9","author":"Sabur","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Agallou, M., Athanasiou, E., Samiotaki, M., Panayotou, G., and Karagouni, E. (2016). Identification of Immunoreactive Leishmania infantum Protein Antigens to Asymptomatic Dog Sera through Combined Immunoproteomics and Bioinformatics Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149894"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-2125.2010.03716.x","article-title":"Proteome mapping of overexpressed membrane-enriched and cytosolic proteins in sodium antimony gluconate (SAG) resistant clinical isolate of Leishmania donovani","volume":"70","author":"Kumar","year":"2010","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.molbiopara.2013.06.006","article-title":"Comparative proteomic analysis of antimony-resistant and -susceptible Leishmania braziliensis and Leishmania infantum chagasi lines","volume":"190","author":"Matrangolo","year":"2013","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/mmi.12639","article-title":"The Leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status","volume":"93","author":"Yau","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ijpddr.2014.05.002","article-title":"Quantitative proteomic analysis of amphotericin B resistance in Leishmania infantum","volume":"4","author":"Brotherton","year":"2014","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jprot.2014.02.030","article-title":"A quantitative proteomic screen to identify potential drug resistance mechanism in alpha-difluoromethylornithine (DFMO) resistant Leishmania donovani","volume":"102","author":"Singh","year":"2014","journal-title":"J. Proteom."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/pim.12189","article-title":"Immunostimulatory potential and proteome profiling of Leishmania donovani soluble exogenous antigens","volume":"37","author":"Kumar","year":"2015","journal-title":"Parasite Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.molbiopara.2014.07.001","article-title":"Shotgun proteomics to unravel the complexity of the Leishmania infantum exoproteome and the relative abundance of its constituents","volume":"195","author":"Braga","year":"2014","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jprot.2009.08.006","article-title":"Proteomic characterization of the released\/secreted proteins of Leishmania (Viannia) braziliensis promastigotes","volume":"73","author":"Cuervo","year":"2009","journal-title":"J. Proteom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1016\/j.vaccine.2007.02.083","article-title":"Long-lasting protection against canine visceral leishmaniasis using the LiESAp-MDP vaccine in endemic areas of France: Double-blind randomised efficacy field trial","volume":"25","author":"Lemesre","year":"2007","journal-title":"Vaccine"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gupta, R., Kumar, V., Kushawaha, P.K., Tripathi, C.P., Joshi, S., Sahasrabuddhe, A.A., Mitra, K., Sundar, S., Siddiqi, M.I., and Dube, A. (2014). Characterization of glycolytic enzymes\u2014rAldolase and rEnolase of Leishmania donovani, identified as Th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086073"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1016\/j.vaccine.2018.03.027","article-title":"Immunotherapeutic potential of Leishmania (Leishmania) donovani Th1 stimulatory proteins against experimental visceral leishmaniasis","volume":"36","author":"Keerti","year":"2018","journal-title":"Vaccine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.actatropica.2017.03.008","article-title":"Probing the efficacy of a heterologous Leishmania\/L. Viannia braziliensis recombinant enolase as a candidate vaccine to restrict the development of L. infantum in BALB\/c mice","volume":"171","author":"Santos","year":"2017","journal-title":"Acta Trop."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.vaccine.2014.01.024","article-title":"Immunization with the Leishmania infantum recombinant cyclophilin protein 1 confers partial protection to subsequent parasite infection and generates specific memory T cells","volume":"32","author":"Rodrigues","year":"2014","journal-title":"Vaccine"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Agallou, M., Margaroni, M., Kotsakis, S.D., and Karagouni, E. (2020). A Canine-Directed Chimeric Multi-Epitope Vaccine Induced Protective Immune Responses in BALB\/c Mice Infected with Leishmania infantum. Vaccines, 8.","DOI":"10.3390\/vaccines8030350"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jconrel.2023.03.006","article-title":"A liposomal vaccine promotes strong adaptive immune responses via dendritic cell activation in draining lymph nodes","volume":"356","author":"Agallou","year":"2023","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Agallou, M., Margaroni, M., Athanasiou, E., Toubanaki, D.K., Kontonikola, K., Karidi, K., Kammona, O., Kiparissides, C., and Karagouni, E. (2017). Identification of BALB\/c Immune Markers Correlated with a Partial Protection to Leishmania infantum after Vaccination with a Rationally Designed Multi-epitope Cysteine Protease A Peptide-Based Nanovaccine. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005311"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.20061141","article-title":"Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis","volume":"204","author":"Nylen","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.4049\/jimmunol.179.5.3161","article-title":"SIR2-deficient Leishmania infantum induces a defined IFN-gamma\/IL-10 pattern that correlates with protection","volume":"179","author":"Silvestre","year":"2007","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.7150\/ijbs.7.1093","article-title":"IL-10-IFN-gamma double producers CD4+ T cells are induced by immunization with an amastigote stage specific derived recombinant protein of Trypanosoma cruzi","volume":"7","author":"Satoskar","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.4049\/jimmunol.1202801","article-title":"Live attenuated Leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in BALB\/c mice","volume":"190","author":"Dey","year":"2013","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S1473-3099(06)70577-1","article-title":"The two faces of interleukin 10 in human infectious diseases","volume":"6","author":"Mege","year":"2006","journal-title":"Lancet. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1128\/IAI.00086-07","article-title":"Memory CD4 T cells enhance primary CD8 T-cell responses","volume":"75","author":"Krawczyk","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1126\/science.1082305","article-title":"Requirement for CD4 T cell help in generating functional CD8 T cell memory","volume":"300","author":"Shedlock","year":"2003","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6350","DOI":"10.4049\/jimmunol.178.10.6350","article-title":"Requirement for CD4 T cell help in maintenance of memory CD8 T cell responses is epitope dependent","volume":"178","author":"Ramsburg","year":"2007","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"De Brito, R.C.F., Cardoso, J.M.O., Reis, L.E.S., Mathias, F.A.S., Aguiar-Soares, R.D.O., Teixeira-Carvalho, A., Roatt, B.M., Correa-Oliveira, R., Ruiz, J.C., and Resende, D.M. (2019). Synthetic Peptides Elicit Strong Cellular Immunity in Visceral Leishmaniasis Natural Reservoir and Contribute to Long-Lasting Polyfunctional T-Cells in BALB\/c Mice. Vaccines, 7.","DOI":"10.3390\/vaccines7040162"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1128\/CVI.00251-16","article-title":"Optimizing Immunization Strategies for the Induction of Antigen-Specific CD4 and CD8 T Cell Responses for Protection against Intracellular Parasites","volume":"23","author":"Hofmeyer","year":"2016","journal-title":"Clin. Vaccine Immunol. CVI"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.4049\/jimmunol.1302806","article-title":"Longitudinal requirement for CD4+ T cell help for adenovirus vector-elicited CD8+ T cell responses","volume":"192","author":"Provine","year":"2014","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nri3567","article-title":"Human memory T cells: Generation, compartmentalization and homeostasis","volume":"14","author":"Farber","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nm1592","article-title":"Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major","volume":"13","author":"Darrah","year":"2007","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1016\/j.vaccine.2009.02.079","article-title":"Leishmania infantum sterol 24-c-methyltransferase formulated with MPL-SE induces cross-protection against L. major infection","volume":"27","author":"Goto","year":"2009","journal-title":"Vaccine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/ni832","article-title":"Distinct lineages of T(H)1 cells have differential capacities for memory cell generation in vivo","volume":"3","author":"Wu","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/nm1108","article-title":"Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites","volume":"10","author":"Zaph","year":"2004","journal-title":"Nat. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: Implications for vaccine design","volume":"8","author":"Seder","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4306","DOI":"10.4049\/jimmunol.145.12.4306","article-title":"Tumor necrosis factor-alpha synergizes with IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide","volume":"145","author":"Liew","year":"1990","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/eji.1830200528","article-title":"Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes","volume":"20","author":"Bogdan","year":"1990","journal-title":"Eur. J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1084\/jem.20061886","article-title":"CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis","volume":"204","author":"Anderson","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/eji.200635937","article-title":"Distinct roles for IL-6 and IL-12p40 in mediating protection against Leishmania donovani and the expansion of IL-10+ CD4+ T cells","volume":"36","author":"Stager","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17123","DOI":"10.1073\/pnas.0904955106","article-title":"A human IL10 BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome","volume":"106","author":"Ranatunga","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"262","DOI":"10.4049\/jimmunol.1203518","article-title":"Leishmania-infected MHC class IIhigh dendritic cells polarize CD4+ T cells toward a nonprotective T-bet+ IFN-gamma+ IL-10+ phenotype","volume":"191","author":"Resende","year":"2013","journal-title":"J. Immunol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/8\/1384\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:37:33Z","timestamp":1760128653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/8\/1384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,19]]},"references-count":72,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["vaccines11081384"],"URL":"https:\/\/doi.org\/10.3390\/vaccines11081384","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,19]]}}}