Abstract
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.
Highlights
Visceral leishmaniasis (VL) is considered one of the most neglected of all the neglected diseases with endemic nature expanding in many peri-urban and urban areas of Brazil, Latin America, Europe, and other areas of the world [1, 2]
A current problem that has worsened the situation of VL in the world is associated with the large number of non-responders patients to conventional chemotherapy with antimony, suggesting the emergence of resistant strains of the parasite [41]
There is a regional variation in the response to treatment in VL patients, and recommendations for the use of conventional drugs may vary in different regions of the world [42]
Summary
Visceral leishmaniasis (VL) is considered one of the most neglected of all the neglected diseases with endemic nature expanding in many peri-urban and urban areas of Brazil, Latin America, Europe, and other areas of the world [1, 2]. In an attempt to control the disease, many strategies are used to interrupt parasite transmission, including elimination of seropositive dogs that act as reservoirs, use of insecticides for vector control and systematic treatment of human cases [3, 4]. The situation is even more complicated by the imminent emergence of resistant parasites to presently available anti-leishmanial drugs, mainly with monotherapy (miltefosine and paromomycin) [11]. There is an urgent need to improve current drugs and promote investment in the discovery of new treatment schemes such as vaccines or immunomodulators (immunotherapy) to promptly induce an effective and protective immune response against the parasite [10]
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