2026-06-14T03:28:58Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/74082025-04-29T13:36:17Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud author Barbosa Santos, Micheli Luize author Nico, Dirlei author Alvisi de Oliveira, Fabrícia author Silva Barreto, Aline author Palatnik-de-Sousa, Iam author Carrillo, Eugenia author Moreno, Javier author Mello de Luca, Paula author Morrot, Alexandre author Santoro Rosa, Daniela author Palatnik, Marcos author Bani-Corrêa, Cristiane author Pacheco de Almeida, Roque author Palatnik-de-Sousa, Clarisa Beatriz funder National Council for Scientific and Technological Development (Brasil) funder Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro funder Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil) 2019-03-27T12:39:42Z 2019-03-27T12:39:42Z 2017-03 Front Immunol. 2017 Mar;8:227. 10.3389/fimmu.2017.00227 1664-3224 Frontiers in immunology 28321221 http://hdl.handle.net/20.500.12105/7408 Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the Leishmania donovani nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains. As markers of VL resistance, the F2 induced the highest levels of IFN-γ, IL-1β, and TNF-α and, together with F1, the strongest secretion of IL-17, IL-6, and IL-10 in DTH+ and cured subjects. F2 also promoted the highest frequencies of CD3+CD4+IL-2+TNF-α-IFN-γ-, CD3+CD4+IL-2+TNF-α+IFN-γ-, CD3+CD4+IL-2+TNF-α-IFN-γ+, and CD3+CD4+IL-2+TNF-α+IFN-γ+ T cells in cured and asymptomatic subjects. Consistent with this, the IFN-γ increase was correlated with decreased spleen (R = -0.428, P = 0.05) and liver sizes (R = -0.428, P = 0.05) and with increased hematocrit counts (R = 0.532, P = 0.015) in response to F1 domain, and with increased hematocrit (R = 0.512, P 0.02) and hemoglobin counts (R = 0.434, P = 0.05) in response to F2. Additionally, IL-17 increases were associated with decreased spleen and liver sizes in response to F1 (R = -0.595, P = 0.005) and F2 (R = -0.462, P = 0.04). Conversely, F1 and F3 increased the CD3+CD8+IL-2+TNF-α-IFN-γ-, CD3+CD8+IL-2+TNF-α+IFN-γ-, and CD3+CD8+IL-2+TNF-α+IFN-γ+ T cell frequencies of VL patients correlated with increased spleen and liver sizes and decreased hemoglobin and hematocrit values. Therefore, cure and acquired resistance to VL correlate with the CD4+-Th1 and Th-17 T-cell responses to F2 and F1 domains. Clinical VL outcomes, by contrast, correlate with CD8+ T-cell responses against F3 and F1, potentially involved in control of the early infection. The in silico-predicted NH36 epitopes are conserved and bind to many HL-DR and HLA and B allotypes. No human vaccine against Leishmania is available thus far. In this investigation, we identified the NH36 domains and epitopes that induce CD4+ and CD8+ T cell responses, which could be used to potentiate a human universal T-epitope vaccine against leishmaniasis. eng Leishmania donovani Leishmania infantum chagasi T cell epitopes Epitope vaccine design Human visceral leishmaniasis Nucleoside hydrolase Recombinant domains Leishmania donovani Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis research article 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 URL https://repisalud.isciii.es/bitstreams/189395de-172b-49cb-b399-ef032262cf42/download File MD5 4bc221dd137370f12f97d0ad1f30a4c5 9726683 application/pdf LeishmaniaDonovaniNucleosideHidrolase_2017.pdf URL https://repisalud.isciii.es/bitstreams/92f1dbe1-e4cb-42a0-9380-bca9894edf9a/download File MD5 800d11017097c778417854cef4e5f813 102847 text/plain LeishmaniaDonovaniNucleosideHidrolase_2017.pdf.txt