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Phase I and II Clinical Trial Comparing the LBSap, Leishmune^®, and Leish-Tec^® Vaccines against Canine Visceral Leishmaniasis.

ABSTRACT: In this study, we performed a phase I and II clinical trial in dogs to evaluate the toxicity and immunogenicity of LBSap-vaccine prototype, in comparison to Leishmune^® and Leish-Tec^® vaccines. Twenty-eight dogs were classified in four groups: (i) control group received 1 mL of sterile 0.9% saline solution; (ii) LBSap group received 600 ?g of Leishmania braziliensis promastigotes protein and 1 mg of saponin adjuvant; (iii) Leishmune^®; and (iv) Leish-Tec^®. The safety and toxicity of the vaccines were measured before and after three immunizations by clinical, biochemical, and hematological parameters. The clinical examinations revealed that some dogs of LBSap and Leishmune^® groups presented changes at the site of vaccination inoculum, such as nodules, mild edema, and local pain, which were transient and disappeared seventy-two hours after vaccination, but these results indicate that adverse changes caused by the immunizations are tolerable. The immunogenicity results demonstrate an increase of B lymphocytes CD21⁺ regarding the Leishmune^® group and monocytes CD14⁺ concerning LBSap and Leishmune^® groups. In the in vitro analyses, an increase in lymphoproliferative activity in LBSap and Leishmune^® groups was observed, with an increase of antigen-specific CD4⁺ and CD8⁺ T lymphocytes in the LBSap group. A second approach of in vitro assays aimed at evaluating the percentage of antigen-specific CD4⁺ and CD8⁺ T lymphocytes producers of IFN-? and IL-4, where an increase in both IFN-? producing subpopulations in the LBSap group was observed, also showed an increase in IFN-? producers in CD8⁺ lymphocytes in the Leish-Tec^® group. Our data regarding immunogenicity indicate that the vaccination process, especially with the LBSap vaccine, generated a protective immune response compatible with L. infantum parasite control. Based on the foregoing, the LBSap vaccine would be suitable for further studies of phase III clinical trial in endemic areas with high prevalence and incidence of canine visceral leishmaniasis (VL) cases.

SUBMITTER: Aguiar-Soares RDO

PROVIDER: S-EPMC7712644 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Phase I and II Clinical Trial Comparing the LBSap, Leishmune®, and Leish-Tec® Vaccines against Canine Visceral Leishmaniasis.

Aguiar-Soares Rodrigo Dian de Oliveira RDO Roatt Bruno Mendes BM Mathias Fernando Augusto Siqueira FAS Reis Levi Eduardo Soares LES Cardoso Jamille Mirelle de Oliveira JMO Brito Rory Cristiane Fortes de RCF Ker Henrique Gama HG Corrêa-Oliveira Rodrigo R Giunchetti Rodolfo Cordeiro RC Reis Alexandre Barbosa AB

Vaccines 20201117 4

In this study, we performed a phase I and II clinical trial in dogs to evaluate the toxicity and immunogenicity of LBSap-vaccine prototype, in comparison to Leishmune® and Leish-Tec® vaccines. Twenty-eight dogs were classified in four groups: (i) control group received 1 mL of sterile 0.9% saline solution; (ii) LBSap group received 600 μg of Leishmania braziliensis promastigotes protein and 1 mg of saponin adjuvant; (iii) Leishmune®; and (iv) Leish-Tec<sup ...[more]

PMID: 33212786

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Project description:In 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.In 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.When 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-?, and IFN-?. 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 %).The 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.

Project description:BackgroundBecause domestic dogs are reservoir hosts for visceral leishmaniasis (VL) in Brazil, one of the approaches used to reduce human disease incidence is to cull infected dogs. However, the results of controlled intervention trials based on serological screening of dogs and killing of seropositive animals are equivocal. A prophylactic vaccine to protect dogs from being infectious to the sand fly vector could be an effective strategy to provide sustained control. Here, we investigated whether a currently licensed commercial subunit rA2 protein-saponin vaccine (Leish-tec®) had an additional effect to dog culling on reducing the canine infectious populations.Methodology/principal findingsThis prospective study was conducted in an L. infantum highly endemic area of southeast Brazil. At the onset of the intervention, all of the eligible dogs received through subcutaneous route a three-dose vaccine course at 21-day intervals and a booster on month 12. For the purpose of comparison, newly recruited healthy dogs were included as the exposed control group. To ascertain vaccine-induced protection, dogs were screened on clinical and serological criteria every 6 months for a 2-year follow-up period. Antibody-based tests and histopathological examination of post-mortem tissue specimens from euthanized animals were used as a marker of infection. The standardized vaccine regime, apart from being safe, was immunogenic as immunized animals responded with a pronounced production of anti-A2-specific IgG antibodies. It should be noted the mean seroconversion time for infection obtained among immunized exposed dogs (~ 18 months), which was twice as high as that for unvaccinated ones (~ 9 months). After two transmission cycles completed, the cumulative incidence of infection did differ significantly (P = 0.016) between the vaccinated (27%) and unvaccinated (42%) dogs. However, the expected efficacy for the vaccine in inducing clinical protection was not evident since 43% of vaccine recipients developed disease over time. Our estimates also indicated that immunoprophylaxis by Leish-tec® vaccine in addition to dog culling might not have an impact on bringing down the incidence of canine infection with L. infantum in areas of high transmission rates.Conclusions/significanceLeish-tec® as a prophylactic vaccine showed promise but needs to be further optimized to be effective in dogs under field conditions, and thereby positively impacts human incidence.

Dataset Information

Phase I and II Clinical Trial Comparing the LBSap, Leishmune^®, and Leish-Tec^® Vaccines against Canine Visceral Leishmaniasis.

Publications

Phase I and II Clinical Trial Comparing the LBSap, Leishmune<sup>®</sup>, and Leish-Tec<sup>®</sup> Vaccines against Canine Visceral Leishmaniasis.

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