title: One-year timeline kinetics of cytokine-mediated cellular immunity in dogs vaccinated against visceral leishmaniasis.
abstract: BACKGROUND
  The main control strategy for visceral leishmaniasis in Brazil has been based on the elimination of seropositive dogs, although this is not widely accepted. In this context, the use of a long-lasting protective vaccine against canine visceral leishmaniasis (CVL) has been highly expected. The aim of this work was to determine the timeline kinetics of the cytokine microenvironment derived from circulating leukocytes as supportive immunological biomarkers triggered by Leishmune® vaccine. Cross-sectional kinetic analysis of cellular immunity cytokines was carried out at three times (1, 6 and 12 months) after primovaccination with Leishmune®. In vitro short-term whole blood cultures were stimulated with Leishmania infantum soluble antigen (SLAg). The secreted cytokine signatures and their major sources were determined.
  
  
  RESULTS
  At six months after vaccination, Leishmune® induced an increase in IL-8, IFN-γ, IL-17a and TNF-α levels and a decrease in IL-10. Cytokine signature analysis revealed a shift in the microenvironment towards a pro-inflammatory profile mediated by IL-8 and IFN-γ. Both, CD4(+) (↑TNF-α(+) and ↑IFN-γ (+)) and CD8(+) (↑IL-17a and ↓IL-4) T-cells contributed to the acquired immune responses observed after stimulation with SLAg.
  
  
  CONCLUSIONS
  The changes observed in the cytokine profile suggested that Leishmune® was able to induce an effective response at six months after primovaccination. After one year, it returned to baseline suggesting the need of additional boosting.
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. christianecosta@cpqrr.fiocruz.br.
authors.forename: Christiane
authors.initials: C
authors.lastname: Costa-Pereira
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. marcela.moreira@cpqrr.fiocruz.br.
authors.forename: Marcela L
authors.initials: ML
authors.lastname: Moreira
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. rsoares@cpqrr.fiocruz.br.
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Soares
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. brunomarteleto@hotmail.com.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Marteleto
authors.affiliation: Clínica Veterinária Santo Agostinho, Avenida Amazonas, 2218, 30180-00, Belo Horizonte, MG, Brazil. vitor@pucminas.br.
authors.forename: Vitor M
authors.initials: VM
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. hallaisfranca@gmail.com.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: França-Dias
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. ludynhamc@hotmail.com.
authors.forename: Ludmila M
authors.initials: LM
authors.lastname: Cardoso
authors.affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil. kelvinsonviana@yahoo.com.br.
authors.forename: Kelvinson F
authors.initials: KF
authors.lastname: Viana
authors.affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil. giunchetti@gmail.com.
authors.forename: Rodolfo C
authors.initials: RC
authors.lastname: Giunchetti
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. oamfilho@cpqrr.fiocruz.br.
authors.forename: Olindo A
authors.initials: OA
authors.lastname: Martins-Filho
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou/FIOCRUZ - MG, Av. Augusto de Lima, 1715, 30190-002, Belo Horizonte, MG, Brazil. sobreira@cpqrr.fiocruz.br.
authors.forename: Márcio S S
authors.initials: MS
authors.lastname: Araújo
mesh_terms: D000818:Animals; D015415:Biomarkers; D001938:Brazil / Q000453:epidemiology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004283:Dog Diseases / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D007111:Immunity, Cellular / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000517:prevention & control / Q000662:veterinary*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D016052:Protozoan Vaccines / Q000276:immunology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016052:Protozoan Vaccines