A vaccine therapy for canine visceral leishmaniasis promoted significant improvement of clinical and immune status with reduction in parasite burden.
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2017
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Herein, we evaluated the treatment strategy employing a therapeutic heterologous
vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant
(LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected
by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant
(n = 6) or with a vaccine composed of antigens of L. braziliensis associated 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 an ex vivo analysis 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. Under in vitro conditions, 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.
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Heterologous vaccine therapy, Immunotherapy
Citação
ROATT, B. M. et al. A vaccine therapy for canine visceral leishmaniasis promoted significant improvement of clinical and immune status with reduction in parasite burden. Frontiers in Immunology, v. 8, p. 1-14, 2017. Disponível em: <http://journal.frontiersin.org/article/10.3389/fimmu.2017.00217/full>. Acesso em: 29 ago. 2017.