A Vaccine Therapy for Canine Visceral Leishmaniasis Promoted Significant Improvement of Clinical and Immune Status with Reduction in Parasite Burden.
Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens ofLeishmania braziliensisassociated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected byLeishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n= 6) or with a vaccine composed of antigens ofL. braziliensisassociated with MPL (LBMPL vaccine therapy,n= 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series. The animals were evaluated before (T0) and 90 days after treatment (T90) for their biochemical/hematological, immunological, clinical, and parasitological variables. Our major results showed that the vaccine therapy with LBMPL was able to restore and normalize main biochemical (urea, AST, ALP, and bilirubin) and hematological (erythrocytes, hemoglobin, hematocrit, and platelets) parameters. In addition, in anex vivoanalysis using flow cytometry, dogs treated with LBMPL vaccine showed increased CD3+T lymphocytes and their subpopulations (TCD4+and TCD8+), reduction of CD21+B lymphocytes, increased NK cells (CD5-CD16+) and CD14+monocytes. Underin vitroconditions, the animals developed a strong antigen-specific lymphoproliferation mainly by TCD4+and TCD8+cells; increasing in both TCD4+IFN-γ+and TCD8+IFN-γ+as well as reduction of TCD4+IL-4+and TCD8+IL-4+lymphocytes with an increased production of TNF-α and reduced levels of IL-10. Concerning the clinical signs of canine visceral leishmaniasis, the animals showed an important reduction in the number and intensity of the disease signs; increase body weight as well as reduction of splenomegaly. In addition, the LBMPL immunotherapy also promoted a reduction in parasite burden assessed by real-time PCR. In the bone marrow, we observed seven times less parasites in LBMPL animals compared with MPL group. The skin tissue showed a reduction in parasite burden in LBMPL dogs 127.5 times higher than MPL. As expected, with skin parasite reduction promoted by immunotherapy, we observed a blocking transmission to sand flies in LBMPL dogs with only three positive dogs after xenodiagnosis. The results obtained in this study highlighted the strong potential for the use of this heterologous vaccine therapy as an important strategy for VL treatment.
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, Brazil.
Bruno Mendes
BM
Roatt
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto , Ouro Preto, Minas Gerais , Brazil.
Rodrigo Dian de Oliveira
RD
Aguiar-Soares
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto , Ouro Preto, Minas Gerais , Brazil.
Levi Eduardo Soares
LE
Reis
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto , Ouro Preto, Minas Gerais , Brazil.
Jamille Mirelle de Oliveira
JM
Cardoso
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto , Ouro Preto, Minas Gerais , Brazil.
Fernando Augusto Siqueira
FA
Mathias
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto , Ouro Preto, Minas Gerais , Brazil.
Rory Cristiane Fortes
RC
de Brito
Laboratório de Bioensaios em Leishmania, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia , Uberlândia, Minas Gerais , Brazil.
Sydnei Magno
SM
da Silva
Laboratório de Fisiologia de Insetos Hematófagos, Departamento de Parasitologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil.
Nelder De Figueiredo
NF
Gontijo
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto , Ouro Preto, Minas Gerais , Brazil.
Sidney de Almeida
SA
Ferreira
Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rockville, MD , USA.
Jesus G
JG
Valenzuela
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, Brazil.
Rodrigo
R
Corrêa-Oliveira
Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil.
Rodolfo Cordeiro
RC
Giunchetti
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, Brazil.
Alexandre Barbosa
AB
Reis
L. infantum; canine visceral leishmaniasis; heterologous vaccine therapy; immune response; immunotherapy