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High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection

Published online by Cambridge University Press:  10 September 2018

Gerusa B. Carvalho ,
Lourena E. Costa ,
Daniela P. Lage ,
Fernanda F. Ramos ,
Thaís T. O. Santos ,
Patrícia A. F. Ribeiro ,
Daniel S. Dias ,
Beatriz C. S. Salles ,
Mariana P. Lima  and
Lívia M. Carvalho
...Show all authors
Gerusa B. Carvalho
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Lourena E. Costa
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Daniela P. Lage
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Fernanda F. Ramos
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Thaís T. O. Santos
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Patrícia A. F. Ribeiro
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Daniel S. Dias
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Beatriz C. S. Salles
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Mariana P. Lima
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Lívia M. Carvalho
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, 35.400-000, Ouro Preto, Minas Gerais, Brazil
Ana C. S. Dias
Affiliation:
Laboratório de Nanobiotecnologia, Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Av. Amazonas s/n, Campus Umuarama, Bloco 2E, Sala 248, 38400-902, Uberlândia, Minas Gerais, Brazil
Patrícia T. Alves
Affiliation:
Laboratório de Nanobiotecnologia, Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Av. Amazonas s/n, Campus Umuarama, Bloco 2E, Sala 248, 38400-902, Uberlândia, Minas Gerais, Brazil
Michelle L. Franklin
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Renata A. M. Silva
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Mariana C. Duarte
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Av. Antônio Carlos, 6627, Pampulha, 31270-901, Minas Gerais, Brazil
Daniel Menezes-Souza
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Av. Antônio Carlos, 6627, Pampulha, 31270-901, Minas Gerais, Brazil
Bruno M. Roatt
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, 35.400-000, Ouro Preto, Minas Gerais, Brazil
Miguel A. Chávez-Fumagalli
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil
Luiz Ricardo Goulart
Affiliation:
Laboratório de Nanobiotecnologia, Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Av. Amazonas s/n, Campus Umuarama, Bloco 2E, Sala 248, 38400-902, Uberlândia, Minas Gerais, Brazil Department of Medical Microbiology and Immunology, University of California-Davis, Davis, CA 95616, USA
Antonio L. Teixeira
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Road, Houston, TX 77041, USA
Eduardo A. F. Coelho*
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Belo Horizonte, 30130-100, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Av. Antônio Carlos, 6627, Pampulha, 31270-901, Minas Gerais, Brazil
*
Author for correspondence: Eduardo A. F. Coelho, E-mail: [email protected]
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Abstract

In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.

Keywords

Immune responseLeishmania amazonensisperipheral blood mononuclear cellsphage displaytegumentary leishmaniasisvaccine
Type
Research Article
Information
Parasitology , Volume 146 , Issue 3 , March 2019 , pp. 322 - 332
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Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

Co-senior authors.

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