PMID- 29908151
OWN - NLM
STAT- MEDLINE
DCOM- 20190415
LR  - 20190415
IS  - 1878-1810 (Electronic)
IS  - 1878-1810 (Linking)
VI  - 200
DP  - 2018 Oct
TI  - Vaccination with a CD4(+) and CD8(+) T-cell epitopes-based recombinant chimeric 
      protein derived from Leishmania infantum proteins confers protective immunity 
      against visceral leishmaniasis.
PG  - 18-34
LID - S1931-5244(18)30084-7 [pii]
LID - 10.1016/j.trsl.2018.05.001 [doi]
AB  - Vaccination seems to be the best approach to control visceral leishmaniasis (VL). 
      Resistance against infection is based on the development of a Th1 immune response 
      characterized by the production of interferons-gamma (IFN-gamma), interleukin-12 (IL-12), 
      granulocyte-macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis 
      factor-alpha (TNF-alpha), among others. A number of antigens have been tested as 
      potential targets against the disease; few of them are able to stimulate human 
      immune cells. In the present study, 1 prediction of MHC class I and II 
      molecules-specific epitopes in the amino acid sequences of 3 Leishmania proteins: 
      1 hypothetical, prohibitin, and small glutamine-rich tetratricopeptide 
      repeat-containing proteins, was performed using bioinformatics tools, and a 
      T-cell epitopes-based recombinant chimeric protein was constructed, synthetized 
      and purified to be evaluated in invitro and in vivo experiments. The purified 
      protein was tested regarding its immunogenicity in peripheral blood mononuclear 
      cells (PBMCs) from healthy subjects and VL patients, as well as to its 
      immunogenicity and protective efficacy in a murine model against Leishmania 
      infantum infection. Results showed a Th1 response based on high IFN-gamma and low 
      IL-10 levels derived from in chimera-stimulated PBMCs in both healthy subjects 
      and VL patients. In addition, chimera and/or saponin-immunized mice presented 
      significantly lower parasite burden in distinct evaluated organs, when compared 
      to the controls, besides higher levels of IFN-gamma, IL-2, IL-12, and GM-CSF, and an 
      IgG2a isotype-based humoral response. In addition, the CD4(+) and CD8(+) T-cell 
      subtypes contributed to IFN-gamma production in the protected animals. The results 
      showed the immunogenicity in human cells and the protective efficacy against L. 
      infantum in a murine model, and well indicate that this recombinant chimera can 
      be considered as a promising strategy to be used against human disease.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Dias, Daniel S
AU  - Dias DS
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Ribeiro, Patricia A F
AU  - Ribeiro PAF
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Martins, Vivian T
AU  - Martins VT
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Lage, Daniela P
AU  - Lage DP
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Costa, Lourena E
AU  - Costa LE
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Chavez-Fumagalli, Miguel A
AU  - Chavez-Fumagalli MA
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Ramos, Fernanda F
AU  - Ramos FF
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Santos, Thais T O
AU  - Santos TTO
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Ludolf, Fernanda
AU  - Ludolf F
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil.
FAU - Oliveira, Jamil S
AU  - Oliveira JS
AD  - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, 
      Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
FAU - Mendes, Tiago A O
AU  - Mendes TAO
AD  - Departamento de Bioquimica e Biologia Molecular, Universidade Federal de Vicosa, 
      Vicosa, Minas Gerais, Brazil.
FAU - Silva, Eduardo S
AU  - Silva ES
AD  - Programa de Pos-Graduacao em Biotecnologia, Universidade Federal de Sao Joao 
      Del-Rei, Divinopolis, Minas Gerais, Brazil.
FAU - Galdino, Alexsandro S
AU  - Galdino AS
AD  - Programa de Pos-Graduacao em Biotecnologia, Universidade Federal de Sao Joao 
      Del-Rei, Divinopolis, Minas Gerais, Brazil.
FAU - Duarte, Mariana C
AU  - Duarte MC
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil; Departamento de Patologia Clinica, COLTEC, Universidade 
      Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
FAU - Roatt, Bruno M
AU  - Roatt BM
AD  - Departamento de Patologia Clinica, COLTEC, Universidade Federal de Minas Gerais, 
      Belo Horizonte, Minas Gerais, Brazil.
FAU - Menezes-Souza, Daniel
AU  - Menezes-Souza D
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil; Departamento de Patologia Clinica, COLTEC, Universidade 
      Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
FAU - Teixeira, Antonio L
AU  - Teixeira AL
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil; Neuropsychiatry Program, Department of Psychiatry and 
      Behavioral Sciences, McGovern Medical School, The University of Texas Health 
      Science Center at Houston, Houston, TX, USA; 1941 East Road, Houston, TX, 77041.
FAU - Coelho, Eduardo A F
AU  - Coelho EAF
AD  - Programa de Pos-Graduacao em Ciencias da Saude: Infectologia e Medicina Tropical, 
      Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 
      Minas Gerais, Brazil; Departamento de Patologia Clinica, COLTEC, Universidade 
      Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic 
      address: eduardoferrazcoelho@yahoo.com.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180522
PL  - United States
TA  - Transl Res
JT  - Translational research : the journal of laboratory and clinical medicine
JID - 101280339
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Epitopes)
RN  - 0 (Leishmaniasis Vaccines)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Saponins)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Protozoan/blood
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Disease Models, Animal
MH  - Dogs
MH  - Epitopes/chemistry/immunology
MH  - Female
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-10/biosynthesis
MH  - Leishmania infantum/*immunology
MH  - Leishmaniasis Vaccines/chemistry/*immunology
MH  - Leishmaniasis, Visceral/*prevention & control
MH  - Leukocytes, Mononuclear/immunology
MH  - Male
MH  - Mice
MH  - Protozoan Proteins/immunology
MH  - Recombinant Fusion Proteins/*immunology
MH  - Saponins/immunology
MH  - Th1 Cells/immunology
EDAT- 2018/06/17 06:00
MHDA- 2019/04/16 06:00
CRDT- 2018/06/17 06:00
PHST- 2018/03/19 00:00 [received]
PHST- 2018/05/09 00:00 [revised]
PHST- 2018/05/14 00:00 [accepted]
PHST- 2018/06/17 06:00 [pubmed]
PHST- 2019/04/16 06:00 [medline]
PHST- 2018/06/17 06:00 [entrez]
AID - S1931-5244(18)30084-7 [pii]
AID - 10.1016/j.trsl.2018.05.001 [doi]
PST - ppublish
SO  - Transl Res. 2018 Oct;200:18-34. doi: 10.1016/j.trsl.2018.05.001. Epub 2018 May 
      22.