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Phage-fused epitopes from Leishmania infantum used as immunogenic vaccines confer partial protection against Leishmania amazonensis infection

Published online by Cambridge University Press:  23 June 2015

LOURENA EMANUELE COSTA ,
MIGUEL ANGEL CHÁVEZ-FUMAGALLI ,
VIVIAN TAMIETTI MARTINS ,
MARIANA COSTA DUARTE ,
DANIELA PAGLIARA LAGE ,
MAYARA I. S. LIMA ,
NATHÁLIA CRISTINA DE JESUS PEREIRA ,
MANUEL SOTO ,
CARLOS ALBERTO PEREIRA TAVARES  and
LUIZ RICARDO GOULART
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LOURENA EMANUELE COSTA
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MIGUEL ANGEL CHÁVEZ-FUMAGALLI
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
VIVIAN TAMIETTI MARTINS
Affiliation:
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MARIANA COSTA DUARTE
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
DANIELA PAGLIARA LAGE
Affiliation:
Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MAYARA I. S. LIMA
Affiliation:
Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil
NATHÁLIA CRISTINA DE JESUS PEREIRA
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
MANUEL SOTO
Affiliation:
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain
CARLOS ALBERTO PEREIRA TAVARES
Affiliation:
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
LUIZ RICARDO GOULART
Affiliation:
Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil Department of Medical Microbiology and Immunology, University of California-Davis, Davis, CA, USA
EDUARDO ANTONIO FERRAZ COELHO*
Affiliation:
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
*
*Corresponding author. Laboratório de Biotecnologia Aplicada ao Estudo das Leishmanioses, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31·270-901 Belo Horizonte, Minas Gerais, Brazil. E-mail: eduardoferrazcoelho@yahoo.com.br
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Summary

Two mimotopes of Leishmania infantum identified by phage display were evaluated as vaccine candidates in BALB/c mice against Leishmania amazonensis infection. The epitope-based immunogens, namely B10 and C01, presented as phage-fused peptides; were used without association of a Th1 adjuvant, and they were administered isolated or in combination into animals. Both clones showed a specific production of interferon-gamma (IFN-γ), interleukin-12 (IL-12) and granulocyte/macrophage colony-stimulating factor (GM-CSF) after in vitro spleen cells stimulation, and they were able to induce a partial protection against infection. Significant reductions of parasite load in the infected footpads, liver, spleen, bone marrow and paws’ draining lymph nodes were observed in the immunized mice, in comparison with the control groups (saline, saponin, wild-type and non-relevant clones). Protection was associated with an IL-12-dependent production of IFN-γ, mediated mainly by CD8+ T cells, against parasite proteins. Protected mice also presented low levels of IL-4 and IL-10, as well as increased levels of parasite-specific IgG2a antibodies. The association of both clones resulted in an improved protection in relation to their individual use. More importantly, the absence of adjuvant did not diminish the cross-protective efficacy against Leishmania spp. infection. This study describes for the first time two epitope-based immunogens selected by phage display technology against L. infantum infected dogs sera, which induced a partial protection in BALB/c mice infected with L. amazonensis.

Keywords

Phage displaymimotopesvaccineleishmaniasisTh1 immune response
Type
Research Article
Information
Parasitology , Volume 142 , Issue 10 , September 2015 , pp. 1335 - 1347
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Copyright
Copyright © Cambridge University Press 2015 

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