Synthetic peptides derived from Leishmania proteins and its ability to induce antigen presentation molecules and lymphoproliferation in cell human cells from human volunteers living in Colombia endemic areas.
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1
Universidad Nacional de Colombia, Immunotoxicology Research Group. Faculty of Sciences, Colombia
Leishmaniasis is a parasitic disease caused by protozoa Leishmania, and distributed in about 98 countries around the world. This work was proposed with the aim to approach the problem associated with the rise on incidence and the wide prevalence of the leishmaniasis worldwide, wich make urgent the need to develop efforts in the search for a new strategies (prophylactic or therapeutic) that promotes the control of the disease in endemic areas. So far, there is not any available vaccine to use in humans besides the efforts and the use of different strategies to avoid the disease.
We have focused our project in the evaluation of the antigenicity of synthetic peptides instead the whole recombinant proteins, because the exact evaluation or linear sequences (epitopes) that may direct the immune response to a Th-1 phenotype, besides the batch to batch reproducibility of the first ones. For that purpose, we selected 3 peptides (15-20 mer) derived from each KMP-11 (39110, 19116 and 19114) and LACK proteins (39108, 14609 and 14608), as candidates to vaccines against cutaneous leishmaniasis, using dendritic cells as professional Antigen-Presenting Cells in assays of evaluation of In vitro antigenic presentation. These peptides were taken from regions highly homologs between most Leishmania species and with prediction of binding to most common HLA-DR’s using bioinformatics tools. We used Dendritic Cells (DC) derived from Peripheral blood mononuclear cells (PBMC’s) as presenting antigen cells in vitro in 4 experimental groups: A) individuals with active cutaneous leishmaniasis (n= 9); B) history of leishmaniasis cured after the treatment (n= 4); C) no history of the disease with positive leishmanin skin test (n= 3) and D) no history of the disease with negative leishmanin skin test, as negative controls (n= 11), collecting A, B and C samples in “El Cármen de Chucurí/Santander, Colombia”.
First, we assessed the ability of DC’s of each volunteer to be competent by the expression of HLA-DR molecule in their surface besides the expression of co-stimulatory molecules in DC’s pulsed with unspecific antigens and recombinant protein KMP-11 (gently donated by Manuel Soto-Centro de Biología Molecular "Severo Ochoa"-CBMSO). Second, we determined the ability of each selected peptide (synthetized by Fundación Instituto de Inmunología de Colombia – FIDIC) to induce cellular lymphocyte proliferation.
As results, we determined that the DC`s differentiated in vitro from PBMC`s by the patients included in this study had the ability to express both HLA-DR molecule and CD80 and CD83 molecules after the stimulation with Lipopolisacharide (LPS), Phytohaemagglutinin (PHA), lysate of whole L. panamensis, and rKMP-11, showing that those cells were competent, however there were no differences between the clinical groups. With the assessment of lymphoproliferation, we determined that the peptides 14609 and 14608 derived from LACK protein, had the ability to induce higher Proliferation Indexes (PI) in the Active Leishmaniasis group (A clinical group) than the other groups.
We conclude that 14609 peptide was able to induce DI and PI in the lymphocytes derived from humans, therefore this peptide is a good candidate to keep evaluating in future works.
Acknowledgements
Acnowledgments to research grup "Centro de Bología Molecular Severo Ochoa" and Manuel Soto by the donation of rKMP-11 protein. We thank to "Secretaría de Salud de Santander" by their support in colecting the samples in an endemic area for leishmaniasis.
This project was financed Colciencias (Contract 03092013).
Keywords:
Leishmaniasis,
synthetic peptides,
Dendritic Cells,
Vaccine candidates,
Humans,
KMP-11,
LACK.
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Oral Presentation
Topic:
Infectious and parasitic diseases
Citation:
Florez
MM,
Granados
DS and
Delgado
LG
(2015). Synthetic peptides derived from Leishmania proteins and its ability to induce antigen presentation molecules and lymphoproliferation in cell human cells from human volunteers living in Colombia endemic areas..
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00322
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Received:
31 May 2015;
Published Online:
15 Sep 2015.
*
Correspondence:
PhD. Lucy G Delgado, Universidad Nacional de Colombia, Immunotoxicology Research Group. Faculty of Sciences, Bogotá, Colombia, lgdelgadom@unal.edu.co