Studies on the protective efficacy of second-generation vaccine along with standard antileishmanial drug in Leishmania donovani infected BALB/c mice

Abstract

It is well established that visceral leishmaniasis (VL; also known as Kala azar) causes immunosuppression, and a successful drug treatment is associated with the development of cell-mediated immunity. Therefore combining a drug with an immune enhancer can provide a better approach for the treatment of the disease. Keeping this in mind, the in vivo antileishmanial efficacy of immunochemotherapy was evaluated with the use of a 78 kDa antigen with or without monophosphoryl lipid A (MPL-A) along with a traditional drug sodium stibogluconate (SSG) in Leishmania donovani infected BALB/c mice. Mice were infected intracardially with promastigotes of L. donovani, and 30 days after infection, these animals were given specific immunotherapy (78 kDa/78 kDa+MPL-A) or chemotherapy (SSG) or immunochemotherapy (SSG+78 kDa/SSG+78 kDa+MPL-A). Animals were euthanased on 1, 15 and 30 post-treatment days. The antileishmanial potential of the immunochemotherapy was revealed by significant reduction in the parasite burden (P<0·001). These animals were also found to exhibit increased delayed type hypersensitivity (DTH) responses, higher IgG2a levels, lower IgG1 levels and greater cytokine (IFN-γ and IL-2) concentrations compared with chemotherapy or immunotherapy alone, pointing towards the generation of a strong protective (Th1) type of immune response. Immunochemotherapy with SSG+78 kDa+MPL-A was found to be most effective in protecting mice against VL and therefore can be an alternative option for treatment of VL.

Protective Cellular Immune Response Induction for Cutaneous Leishmaniasis by a New Immunochemotherapy Schedule

“…The present data are supported by literature reports which have shown the advantage of immunochemotherapy over monotherapy both in murine models of cutaneous and visceral leishmaniasis, as well as in patients suffering from American cutaneous leishmaniasis treated with leishmanicidal drugs associated with different Leishmania antigens (56)(57)(58)(59)(60)(61).…”

A recombinant chimeric protein composed of human and mice‐specific CD4+ and CD8+ T‐cell epitopes protects against visceral leishmaniasis

“…Like previously reported, the use of vaccines combining immunogenic proteins could provide benefits in terms of protection efficacy against distinct Leishmania species . However, there are a few studies evaluating multi‐antigenic candidates as vaccine to protect against leishmaniasis, as studies have been developed evaluating single antigens or usually employed these immunogens to protect against one parasite species …”

Immunogenicity and efficacy of recombinant 78 kDa antigen of Leishmania donovani formulated in various adjuvants against murine visceral leishmaniasis

“…After 48 h, the thickness of right and left foot pad was measured using a pair of Vernier calipers. Results were expressed as mean ± SD of percentage increase in the thickness of the right foot-pad as compared to the left footpad of mice [18] .…”

“…96-well ELISA plates were coated with crude antigen. Serum samples were added at twofold serial dilutions, followed by washes and addition of isotype specific HRP-conjugated secondary antibodies (rabbit anti-mouse IgG1 or IgG2a) after which the substrate and chromogen were added and absorbance was read on an ELISA plate reader at 450 nm [18].…”