Recombinant prohibitin protein of Leishmania infantum acts as a vaccine candidate and diagnostic marker against visceral leishmaniasis
Autor: | Danielle F. de Magalhães-Soares, Patrícia A.F. Ribeiro, Áquila S.B. Portela, Daniel Menezes-Souza, Daniela P. Lage, Eduardo Silva, Bethina T. Steiner, Lourena E. Costa, Vívian T. Martins, Daniel Dias, Marcella Rezende Rodrigues, Eduardo A.F. Coelho, Bruno Mendes Roatt, Alexsandro Sobreira Galdino, Beatriz C.S. Salles, Ricardo Andrez Machado-de-Ávila, Mariana C. Duarte, Julia A.G. Silveira, Anna Letícia Teotonio Dias, Fernanda F. Ramos, Miguel A. Chávez-Fumagalli, Rachel B. Caligiorne, Thaís T.O. Santos |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Immunology Antigens Protozoan Serology 03 medical and health sciences Mice Dogs Antigen Prohibitins medicine Animals Humans Prohibitin Leishmania infantum Amastigote Mice Inbred BALB C Vaccines biology Th1 Cells biology.organism_classification medicine.disease Leishmania Virology Recombinant Proteins Repressor Proteins 030104 developmental biology Visceral leishmaniasis biology.protein Leishmaniasis Visceral Antibody |
Zdroj: | Cellular immunology. 323 |
ISSN: | 1090-2163 |
Popis: | Visceral leishmaniasis (VL) represents a serious public health problem, as Leishmania infantum is one of main disease causative agents in the Americas. In a previous immunoproteomic study, the prohibitin (PHB) protein was identified in L. infantum promastigote and amastigote extracts by antibodies in asymptomatic and symptomatic VL dog sera. This protein was found to be highly conserved between different Leishmania spp., but it presented a low identity with amino acid sequences of other organisms. The aim of the present study was to evaluate the cellular response induced by the recombinant PHB (rPHB) protein in BALB/c mice, as well as in PBMCs purified from untreated and treated VL patients, as well as to evaluate its protective efficacy against an infection by L. infantum promastigotes. Our data showed that there was a Th1 cellular response to rPHB, based on high levels of IFN-γ, IL-12, and GM-CSF in the immunized animals, as well as a proliferative response specific to the protein and higher IFN-γ levels induced in PBMCs from individuals who had recovered from the disease. The protection was represented by significant reductions in the parasite load in the animals' spleen, liver, bone marrow, and draining lymph nodes, as compared to results found in the control groups. In addition, an anti-rPHB serology, using a canine and human serological panel, showed a high performance of this protein when diagnosing VL based on high sensitivity and specificity values, as compared to results found for the rA2 antigen and the soluble Leishmania antigenic extract. Our data suggest that PHB has a potential application for the diagnosis of canine and human VL through antibody detection, as well as an application as a vaccine candidate to protect against disease. |
Databáze: | OpenAIRE |
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