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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.

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.

Visceral leishmaniasis (VL) is a neglected tropical disease caused by Leishmania donovani or Leishmania infantum. Currently, the patients are treated with chemotherapeutic drugs; however, their toxicity limits their use. It would be desirable to develop a vaccine against this infection. In this study, we assessed the efficacy of different vaccine formulations at variable time points. Heat-killed (HK) antigen of Leishmania donovani was adjuvanted with two adjuvants (AddaVax and Montanide ISA 201) and three immunizations at a gap of 2 weeks (wk) were given to BALB/c mice. After 2 weeks of the last booster, mice were given challenge infection and sacrificed before challenge and after 4wk, 8wk, and 12 wk post-challenge. Significant protective immunity was observed in all the immunized animals and it was indicated by the notable rise in delayed-type hypersensitivity (DTH) response, remarkably declined parasite burden, a significant increase in the levels of interferon-gamma (IFN-γ), interleukin-12, interleukin-17 (Th1 cytokines), and IgG2a in contrast to infected control mice. Montanide ISA 201 with HK antigen provided maximum protection followed by AddaVax with HK and then HK alone. These findings elaborate on the importance of the tested adjuvants in the vaccine formulations against murine visceral leishmaniasis.

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.