Multicomponent LBSap vaccine displays immunological and parasitological profiles similar to those of Leish-Tec® and Leishmune® vaccines against visceral leishmaniasis

Abstract

BackgroundIn past years, many researchers have sought canine visceral leishmaniasis (CVL) prevention through the characterization of Leishmania antigens as vaccine candidates. Despite these efforts, there is still no efficient vaccine for CVL control.MethodsIn the present study, we performed a pre-clinical vaccine trial using BALB/c mice to compare the effects of the multicomponent LBSap vaccine with those of Leish-Tec® and Leishmune®. Blood was collected to determine the frequency of peripheral blood cells and to evaluate hematologic and immunophenotypic parameters. Liver and spleen samples were collected for parasitological quantification, and spleen samples were used to access the cytokine profile.ResultsWhen measuring total IgG and IgG1 anti-Leishmania levels after the third vaccination and L. infantum challenge, it was evident that all vaccines were able to induce humoral immune response. Regarding the innate immune response, increased levels of NK CD3-CD49+ cells were the hallmark of all vaccinated groups, whereas only the Leish-Tec® group displayed a high frequency of CD14+ monocytes after L. infantum challenge. Moreover, CD3+CD4+ T cells were the main circulating lymphocytes induced after L. infantum challenge with all evaluated vaccines. Importantly, after L. infantum challenge, splenocytes from the Leishmune® vaccine produced high levels of IL-2, whereas a prominent type 1 immune response was the hallmark of the LBSap vaccine, which presented high levels of IL-2, IL-6, TNF-α, and IFN-γ. The efficacy analysis using real-time polymerase chain reaction demonstrated a reduction in the parasitism in the spleen (Leishmune®: 64 %; LBSap: 42 %; and Leish-Tec®: 36 %) and liver (Leishmune®: 71 %; LBSap: 62 %; and Leish-Tec®: 48 %).ConclusionsThe dataset led to the conclusion that the LBSap vaccination was able to induce immune and efficacy profiles comparable with those of commercial vaccines, thus demonstrating its potential as a promising vaccine candidate for visceral leishmaniasis control.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1752-6) contains supplementary material, which is available to authorized users.

Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

“…In recent years, many experimental models have been developed and used for VL studies, each with specific characteristics; however, none of these studies accurately reproduces what happens in infected humans. The murine model is comparable to self-controlled oligosymptomatic cases and therefore is useful for the study of the protective immune response; this model has significantly contributed to the understanding of the hypothesis of immune-mediated mechanisms relevant to understand distinct aspects of leishmaniasis, as well as identified relevant elements associated with protective response in chemotherapeutic and immunoprophylactic approaches (11,12). In addition, many studies have used the murine experimental model of VL and produced similar results of pathological, immunological, and parasitological evaluation using different strategies of treatments (immunotherapy and immunochemotherapy) (13)(14)(15)(16).…”

New Vaccine Formulations Containing a Modified Version of the Amastigote 2 Antigen and the Non-Virulent Trypanosoma cruzi CL-14 Strain Are Highly Antigenic and Protective against Leishmania infantum Challenge

“…In addition, both TLRs are activated during L. donovani infection ( 45 ). Of note is the fact that the protection levels induced by the rA2/CpG B297 formulation against experimental VL were higher than those previously described in BALB/c mice immunized with formulations containing saponin, including the commercial Leish-Tec ® vaccine ( 46 ). Although CpGs had emerged as good inducers of Th1 immune responses, the combined formulation with Alum increases the antigen/adjuvant depots, leading to an improved uptake by professional presenting cells, strengthening specific immune responses ( 47 ).…”

The Delay in the Licensing of Protozoal Vaccines: A Comparative History

“…In contrast, a higher potency was described for Leishmune R , which, when used for immunotherapy, gave an 80% reduction in symptomatic cases, a 100% reduction in parasite-positive cases, and a 100% reduction in deaths, and, when used in combination with chemotherapy, also promoted a sterile cure with negative PCR results (111). This evidence explains why many comparatives studies disclosed results of higher efficacy for Leishmune R than for Leishtec R and/or LBsap vaccines (124,125) as well as a stronger induction of the immune and pro-inflammatory response (126)(127)(128) and enhancement of the proportions of CD8 + T cells secreting-IFN-γ (129).…”