{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:34:36Z","timestamp":1791488076223,"version":"4.3.4"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306498\/2022-7, 304764\/2018-3"],"award-info":[{"award-number":["306498\/2022-7, 304764\/2018-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/200.788\/2020, E-26\/202.903\/2017, E-26\/200.887\/2021, E-26\/204.074\/2024, E-26\/010002419\/2019"],"award-info":[{"award-number":["E-26\/200.788\/2020, E-26\/202.903\/2017, E-26\/200.887\/2021, E-26\/204.074\/2024, E-26\/010002419\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Visceral leishmaniasis (VL) is a severe human vector-borne CD4-immunosuppressive disease that can be lethal if untreated soon after symptoms arise. No vaccine is available against human VL, and its chemotherapy is highly toxic and requires hospitalization. VL patients show substantially decreased CD4<jats:sub>+<\/jats:sub> total and <jats:italic>Leishmania<\/jats:italic>-specific CD4+ T cell counts. <jats:italic>Leishmania (L.) donovani<\/jats:italic> nucleoside hydrolase (NH36) is a DNA metabolism enzyme and a conserved marker of the <jats:italic>Leishmania<\/jats:italic> genus. It has been considered, among other <jats:italic>Leishmania<\/jats:italic> antigens, a vaccine candidate. In mice vaccinated with NH36, protection against VL is mediated by a CD4<jats:sub>+<\/jats:sub> T cell response to the NH36 C-terminal domain (F3), and against cutaneous leishmaniasis (CL), by a CD4+ response against F3 and a CD8+ response against the NH36 N-terminal (F1). Vaccination with a recombinant chimera containing the F1 and F3 domains expressed in tandem (F1F3) protected mice against the heterologous CL infection by <jats:italic>L. (L.) amazonensis<\/jats:italic> and <jats:italic>L. (V.) braziliensis<\/jats:italic>. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this investigation, BALB\/c mice were immunized with either F1, F3, a mixture of both, or with the F1F3 chimera, plus saponin and challenged with amastigotes of <jats:italic>L. (L.) infantum chagasi<\/jats:italic>, the agent of VL in America. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Before and after infection, the F1F3 chimera and the F3 vaccines promoted the highest IgA, IgM, IgG, IgG1, IgG2a, IgG2b, and IgG3 antibody responses. The F1F3 chimera promoted the strongest intradermal response against the leishmanial antigen, the highest body weight gain, and the most potent reduction of the spleen and liver relative weights. In addition, the F1F3 chimera vaccine increased the secretion of IFN-\u03b3, and, together with the F3 vaccine, the secretion of TNF-\u03b1 by splenocytes. The F1F3 chimera and the F1 vaccine also promoted the strongest secretion of IL-10, which was very low in mice immunized with F3. Thus, the IFN-\u03b3\/IL-10 and TNF-\u03b1\/IL-10 ratios, characteristic of a Th1 response, were increased in mice vaccinated with F3. The F1F3 chimera and the F3 vaccine reduced the parasite load in the liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The F1F3 chimera, as described for the heterologous CL infections, also optimizes protection against the homologous visceral leishmaniasis infection by <jats:italic>L. (L.) infantum chagasi<\/jats:italic>, by a Th1 contribution from the F3 peptide and a regulatory response from the F1 peptide. Expression of the F1 and F3 domains <jats:italic>in tandem<\/jats:italic> induced higher efficacy than the simple mixture of the F1 and F3 domains.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1598755","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T08:24:04Z","timestamp":1751358244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The F1F3 recombinant chimera induced higher vaccine efficacy than its independent F1 and F3 components against Leishmania (L.) infantum chagasi mice infection"],"prefix":"10.3389","volume":"16","author":[{"given":"Daniele Crespo","family":"Gomes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paula","family":"Fonseca-Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vinicius","family":"Alves-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisa B.","family":"Palatnik-de-Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"B1","unstructured":"Leishmaniasis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0008468","DOI":"10.1371\/journal.pntd.0008468","article-title":"The potential impact of human visceral leishmaniasis vaccines on population incidence","volume":"14","author":"Le Rutte","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.idc.2018.10.005","article-title":"Visceral leishmaniasis: recent advances in diagnostics and treatment regimens","volume":"33","author":"van Griensven","year":"2019","journal-title":"Infect Dis Clin North Am"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-4-197","article-title":"One Health: the global challenge of epidemic and endemic leishmaniasis","volume":"4","author":"Palatnik-de-Sousa","year":"2011","journal-title":"Parasit Vectors"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-022-07429-3","article-title":"Lethality among individuals infected with visceral leishmaniasis in Brazil: a retrospective study (2007-2018)","volume":"121","author":"Carvalho","year":"2022","journal-title":"Parasitol Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet Lond Engl"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00813","article-title":"Nucleoside hydrolase NH 36: A vital enzyme for the leishmania genus in the development of T-cell epitope cross-protective vaccines","volume":"10","author":"Palatnik-de-Sousa","year":"2019","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703678104","article-title":"Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy","volume":"104","author":"Lukes","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.03.006","article-title":"Towards multilocus sequence typing of the Leishmania donovani complex: resolving genotypes and haplotypes for five polymorphic metabolic enzymes (ASAT, GPI, NH1, NH2, PGD)","volume":"36","author":"Mauricio","year":"2006","journal-title":"Int J Parasitol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00100","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":"Alves-Silva","year":"2017","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00227","article-title":"Leishmania donovani nucleoside hydrolase (NH36) domains induce T-cell cytokine responses in human visceral leishmaniasis","volume":"8","author":"Barbosa Santos","year":"2017","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1038\/cti.2015.6","article-title":"From mouse to man: safety, immunogenicity and efficacy of a candidate leishmaniasis vaccine LEISH-F3+GLA-SE","volume":"4","author":"Coler","year":"2015","journal-title":"Clin Transl Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(01)00768-5","article-title":"A nonspecific nucleoside hydrolase from Leishmania donovani: implications for purine salvage by the parasite","volume":"280","author":"Cui","year":"2001","journal-title":"Gene"},{"key":"B14","unstructured":"BLAST: basic local alignment search tool"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e866","DOI":"10.1371\/journal.pntd.0000866","article-title":"Adaptive immunity against Leishmania nucleoside hydrolase maps its c-terminal domain as the target of the CD4+ T cell-driven protective response","volume":"4","author":"Nico","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00189","article-title":"Cross-Protective Immunity to Leishmania amazonensis is Mediated by CD4+ and CD8+ Epitopes of Leishmania donovani Nucleoside Hydrolase Terminal Domains","volume":"5","author":"Nico","year":"2014","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/j.1747-0285.2009.00825.x","article-title":"Advantages of a synthetic peptide immunogen over\u00a0a\u00a0protein immunogen in the development of an anti-pilus vaccine for Pseudomonas aeruginosa","volume":"74","author":"Kao","year":"2009","journal-title":"Chem Biol Drug Des"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00826","article-title":"Editorial: epitope discovery and\u00a0synthetic vaccine design","volume":"9","author":"Palatnik-de-Sousa","year":"2018","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0012757","DOI":"10.1371\/journal.pntd.0012757","article-title":"Efficacy of vaccines based on chimeric or multiepitope antigens for protection against visceral leishmaniasis: A systematic review","volume":"18","author":"Lopes","year":"2024","journal-title":"PLoS Negl Trop Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.0141-9838.2004.00711.x","article-title":"Adjuvant guided polarization of the immune humoral response against a protective multicomponent antigenic protein (Q) from Leishmania infantum. A CpG + Q mix protects Balb\/c mice from infection","volume":"26","author":"Parody","year":"2004","journal-title":"Parasite Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.02.111","article-title":"A large-scale field randomized trial demonstrates safety and efficacy of the vaccine LetiFend\u00ae against canine leishmaniosis","volume":"36","author":"Fern\u00e1ndez Cotrina","year":"2018","journal-title":"Vaccine"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00724","article-title":"The F1F3 Recombinant Chimera of Leishmania donovani-Nucleoside Hydrolase (NH36) and Its Epitopes Induce Cross-Protection Against Leishmania (V.) Braziliensis Infection in Mice","volume":"10","author":"Alves-Silva","year":"2019","journal-title":"Front Immunol"},{"key":"B23","article-title":"Regulation of Leishmania populations within the host. I. @ the variable course of Leishmania donovani infections in mice","volume":"30","author":"Bradley","year":"1977","journal-title":"Clin Exp Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00967","article-title":"NH36 and F3 antigen-primed dendritic cells show preserved migrating capabilities and CCR7 expression and F3 is effective in immunotherapy of visceral leishmaniasis","volume":"9","author":"Nico","year":"2018","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/s0264-410x(02)00444-9","article-title":"Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis","volume":"21","author":"Santos","year":"2002","journal-title":"Vaccine"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/antib8040057","article-title":"IgA: structure, function, and developability","volume":"8","author":"de Sousa-Pereira","year":"2019","journal-title":"Antibodies (Basel)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1486407","article-title":"The development and maintenance of immunity against visceral leishmaniasis","volume":"15","author":"Tiwari","year":"2024","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00131-10","article-title":"Correlates of protection induced by vaccination","volume":"17","author":"Plotkin","year":"2010","journal-title":"Clin Vaccine Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.11.061","article-title":"The FML-vaccine (Leishmune) against canine visceral leishmaniasis: a transmission blocking vaccine","volume":"24","author":"Saraiva","year":"2006","journal-title":"Vaccine"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.7.6.833","article-title":"FML vaccine against canine visceral leishmaniasis: from second-generation to synthetic vaccine","volume":"7","author":"Palatnik-de-Sousa","year":"2008","journal-title":"Expert Rev Vaccines"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2021.1878028","article-title":"Transmission-blocking vaccines: harnessing herd immunity for malaria elimination","volume":"20","author":"Duffy","year":"2021","journal-title":"Expert Rev Vaccines"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.152905","article-title":"Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review","volume":"60","author":"Lacaille-Dubois","year":"2019","journal-title":"Phytomedicine"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1681","article-title":"The perfect mix: recent progress in adjuvant research","volume":"5","author":"Guy","year":"2007","journal-title":"Nat Rev Microbiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2018.03.005","article-title":"Elucidating the mechanisms of action of saponin-derived adjuvants","volume":"39","author":"Marciani","year":"2018","journal-title":"Trends Pharmacol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.01.072","article-title":"Protective vaccination against murine visceral leishmaniasis using aldehyde-containing Quillaja saponaria sapogenins","volume":"22","author":"Palatnik de Sousa","year":"2004","journal-title":"Vaccine"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2012.12-0180","article-title":"Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi","volume":"87","author":"Stober","year":"2012","journal-title":"Am J Trop Med Hyg"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e1687","DOI":"10.1371\/journal.pntd.0001687","article-title":"Immunodominant antigens of Leishmania chagasi associated with protection against human visceral leishmaniasis","volume":"6","author":"Ab\u00e1nades","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-261","article-title":"Resistance to visceral leishmaniasis is severely compromised in mice deficient of bradykinin B2-receptors","volume":"5","author":"Nico","year":"2012","journal-title":"Parasit Vectors"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2020.104272","article-title":"IFN-\u03b3+ CD4+ T cell-driven prophylactic potential of recombinant LDBPK_252400 hypothetical protein of Leishmania donovani against visceral leishmaniasis","volume":"361","author":"Yadav","year":"2021","journal-title":"Cell Immunol"},{"key":"B40","doi-asserted-by":"publisher","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":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.773983","article-title":"Multifunctional, TNF-\u03b1 and IFN-\u03b3-secreting CD4 and CD8 T cells and CD8High T cells are associated with the cure of human visceral leishmaniasis","volume":"12","author":"Rodrigues","year":"2021","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2023.139600","article-title":"Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in adipose tissue of women from Grand Tunis and their association with demographic factors and dietary habits","volume":"338","author":"Achour","year":"2023","journal-title":"Chemosphere"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1277557","article-title":"CD4+ Th1 and Th17 responses and multifunctional CD8 T lymphocytes associated with cure or disease worsening in human visceral leishmaniasis","volume":"15","author":"de Franca","year":"2024","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/s0171-2985(11)80192-0","article-title":"Generation of cytokines in human visceral leishmaniasis: dissociation of endogenous TNF-\u03b1 and IL-1\u03b2 Production","volume":"183","author":"Zwingenberger","year":"1991","journal-title":"Immunobiology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4334","DOI":"10.1038\/s41598-017-04595-8","article-title":"Anti-parasite therapy drives changes in human visceral leishmaniasis-associated inflammatory balance","volume":"7","author":"Ara\u00fajo-Santos","year":"2017","journal-title":"Sci Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03171.x","article-title":"Mixed inflammatory\/regulatory cytokine profile marked by simultaneous raise of interferon-gamma and interleukin-10 and low frequency of\u00a0tumour necrosis factor-alpha(+) monocytes are hallmarks of active human visceral Leishmaniasis due to Leishmania chagasi infection","volume":"146","author":"Peruhype-Magalh\u00e3es","year":"2006","journal-title":"Clin Exp Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e0004375","DOI":"10.1371\/journal.pntd.0004375","article-title":"The severity of visceral leishmaniasis correlates with elevated levels of serum IL-6, IL-27 and sCD14","volume":"10","author":"Dos Santos","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1590\/s0036-46651998000100007","article-title":"Presence of circulating levels of interferon-gamma, interleukin-10 and tumor necrosis factor-alpha in patients with visceral leishmaniasis","volume":"40","author":"de Medeiros","year":"1998","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/163.4.853","article-title":"Tumor necrosis factor (cachectin) in human visceral leishmaniasis","volume":"163","author":"Barral-Netto","year":"1991","journal-title":"J Infect Dis"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00670","article-title":"Cytokines: key determinants of resistance or disease progression in visceral leishmaniasis: opportunities for novel diagnostics and immunotherapy","volume":"10","author":"Dayakar","year":"2019","journal-title":"Front Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8845826","article-title":"A Chimera of Th1 Stimulatory Proteins of Leishmania donovani Offers Moderate Immunotherapeutic Efficacy with a Th1-Inclined Immune Response against Visceral Leishmaniasis","volume":"2021","author":"Ratnapriya","year":"2021","journal-title":"BioMed Res Int"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00750","article-title":"F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis","volume":"8","author":"Carrillo","year":"2017","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1590\/0037-8682-0203-2013","article-title":"Severe visceral leishmaniasis in children: the relationship between cytokine patterns and clinical features","volume":"46","author":"Gama","year":"2013","journal-title":"Rev Soc Bras Med Trop"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e12535","DOI":"10.1111\/pim.12535","article-title":"An IL-10 dominant polarization of monocytes is a feature of Indian Visceral Leishmaniasis","volume":"40","author":"Roy","year":"2018","journal-title":"Parasite Immunol"},{"key":"B55","doi-asserted-by":"publisher","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":"Nyl\u00e9n","year":"2007","journal-title":"J Exp Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir461","article-title":"IL-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis","volume":"204","author":"Gautam","year":"2011","journal-title":"J Infect Dis"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb7100011","article-title":"Balancing immunity and pathology in visceral leishmaniasis","volume":"85","author":"Stanley","year":"2007","journal-title":"Immunol Cell Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1540537","article-title":"Design and development of highly conserved, HLA-promiscuous T cell multiepitope vaccines against human visceral Leishmaniasis","volume":"16","author":"Barreto","year":"2025","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00813","article-title":"Nucleoside hydrolase NH 36: A vital enzyme for the leishmania genus in the development of T-cell epitope cross-protective vaccines","volume":"10","author":"Palatnik-de-Sousa","year":"2019","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1598755\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T08:24:05Z","timestamp":1751358245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1598755\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":59,"alternative-id":["10.3389\/fimmu.2025.1598755"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1598755","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"article-number":"1598755"}}