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The menace of the enfeebling disease leishmaniasis prevails due to the inaccessibility of effective vaccine and chemotherapy. Hence in the pursuit of finding novel alternative options with reasonable efficacy, immunomodulation, leishmanicidal activity and fewer side effects, screening of compounds from natural sources is needed. This study was focused on in vitro and in vivo antileishmanial screening of gallic acid (GA) against Leishmania donovani infection in BALB/c mice. GA showed in vitro parasiticidal activity and IC50 value of 19.59 ± 0.74 µg/ml and is able to arrest cell cycle at the sub‐G0/G1 phase. The therapeutic potential of gallic acid was assessed in the L. donovani‐infected BALB/c mice. GA reported a reduction in parasite burden and augmentation of CD4+ and CD8+ T lymphocytes. Also, the polarization of mouse immune status to protective Th1 response was evidenced by increased delayed‐type hypersensitivity response and levels of IgG2a, reactive oxygen species and nitric oxide. GA was reported to be safe and non‐toxic to human cell line THP‐1 and also to the liver and kidney of mice. Hence, the findings of the present study indicate the possible role of GA in the strengthening of host immune system and thus facilitating the clearance of leishmanial infection and conferring protection. [ABSTRACT FROM AUTHOR]

Morbid infection of leishmaniasis is posing threat to humankind due to its exacerbating prevalence in newer emerging areas. Moreover, the availability of limited drugs, their toxicity, limited efficacy, the emergence of drug resistance, and unavailability of vaccines are the major obstacles in its elimination. This implies the demand for a prophylactic vaccine candidate to prevent this infection and resulting fatal disease. We evaluated gardiquimod (a toll-like receptor-7 agonist) for its action as an adjuvant with the heat-killed antigen of Leishmania donovani. BALB/c mice were immunized with a vaccine either with or without adjuvant and given challenge infection. The results depicted the low parasite burden, higher delayed-type hypersensitivity response, and higher levels of IgG2a, Th1 cytokines, and NO in immunized mice in contrast to infected control mice. Low levels of Th2 cytokines and IgG1 were also noticed in the vaccinated mice than in infected mice. The mice immunized with a combination of gardiquimod and heat-killed antigen showed maximum efficacy. The results from the present study reflect the potential of tested vaccine candidate with gardiquimod as an adjuvant. • DTH response was generated in response to vaccination in mice with heat-killed antigen along with TLR-7 agonist gardiquimod. • Immunized animals were protected against L. donovani infection through the genration of humoral and cellular immunity. • Reduced parasite burden was observed in animals immunized with adjuvanted vaccine. • First report depicting the potential of TLR-7 agonist gardiquimod as an adjuvant in visceral Leishmania vaccine. [ABSTRACT FROM AUTHOR]

Tropical and subtropical areas of the world are affected by leishmaniasis, which is caused by Leishmania spp. It has been categorized as an NTD (neglected tropical disease) because of its negligence. The sand fly of genus Phlebotomus acts as the vector for the transmission of the promastigote form of this protozoan parasite to the mammalian host where it converts to amastigote form in the macrophages. Visceral form of leishmaniasis (VL) is a deadly infection in the endothelial system of the human and other mammals. Only a few chemotherapeutic agents are available for the treatment of this infectious disease whereas no vaccine is available for the control of leishmanial infection. Therefore in the current study, we have tested the effects of gardiquimod (a TLR agonist) as an adjuvant in combination with the formalin-killed antigen of L. donovani as a vaccine. The mice were vaccinated thrice at an interval of 2 weeks and challenged with L. donovani promastigotes after 2 weeks of the last vaccination. We assessed the parasite load, delayed-type hypersensitivity (DTH) responses, humoral and cell-mediated immune response in BALB/c mice before and after challenge infection with L. donovani. Immunized mice were found to have the least parasite load, high DTH response, elevated levels of Th1 cytokines, IgG2a, and nitric oxide than non-immunized and infected control mice. The efficacy of the vaccine was boosted with the use of adjuvant gardiquimod that depicts its potential as an adjuvant in this study. Our study is reporting the adjuvant effects of gardiquimod for the first time. Further studies using other Leishmania species can be performed to signify its role. • No vaccine is available to prevent the Leishmania infection. • First report on adjuvant effects of gardiquimod in Leishmania vaccine against visceral leishmaniasis. • Vaccine induced protection was assessed in experimental groups. • Humoral and cell-mediated immune responses were generated in immunized mice. • Parasite burden was least in mice immunized with vaccine adjuvanted with gardiquimod and highest in infected mice. [ABSTRACT FROM AUTHOR]

Kinteoplastid protozoan parasite of genus Leishmania is the pathogen that causes leishmaniasis. Its prevalence is highest after malaria and visceral leishmaniasis is the most dreaded form of infection. No vaccine is available for the disease management and it relies wholly on a few chemotherapeutic agents which are toxic and besides drug resistance their costs are the limitations. Therefore, development of an effective vaccine is urgently required. In this study, Montanide ISA 201 and AddaVax were assessed for their adjuvant potential along with formalin-inactivated or killed vaccine for the immune induction. Immunological and parasitological studies were conducted to evaluate the efficacy of different vaccine formulations in BALB/c mice before challenge infection as well as 4, 8, and 12 weeks after challenge. The efficacy of vaccines was evidenced with reduced parasite burden, the higher DTH response, Th1 cytokines, and IgG2a isotype antibody in immunized mice. All the vaccines showed their potential against Leishmania donovani infection and vaccine formulated with Montanide ISA 201 exhibited maximum efficacy. Our results suggest the potential of these vaccine formulations in controlling Leishmania infection. • Potential of AddaVax and Montanide ISA 201 was assessed with formalin-killed or inactivated antigen of Leishmania donovani. • Th1 skewed immune response was generated in vaccinated BALB/c mice. • Vaccine driven protection was reported in all the immunized groups. • Potential of adjuvants exhibited in vaccines tested against visceral leishmaniasis for the first time. • Montanide ISA 201 incorporated vaccines showed maximum efficacy among all vaccine groups. [ABSTRACT FROM AUTHOR]