Enhanced efficacy and immunogenicity of 78 kDa antigen formulated in various adjuvants against murine visceral leishmaniasis

Abstract

Leishmania infection causes localized cutaneous to severe visceral disease in humans and animals. Current control measures, based on antimonial compounds, are not effective because of resistance in Leishmania. Vaccination would be a feasible alternative, but as yet no vaccine to protect humans against infection has been commercialized. Parasite antigens that preferentially stimulate the induction of significant protection through Th1 response presents a rational approach for a vaccine against leishmaniasis. With this view in mind, we investigated the potential of 78 kDa antigen of Leishmania donovani alone and along with different adjuvants against murine visceral leishmaniasis. Various adjuvants used along with 78 kDa antigen include monophosphoryl lipid A (MPL-A), liposomal encapsulation, recombinant IL-12, autoclaved Leishmania antigen (ALD) and Freund's adjuvant (FCA). BALB/c mice were immunized subcutaneously thrice with respective vaccine formulation. Challenge infection was given intracardially after 2 weeks of second booster. A significant decrease in parasite burden was seen in vaccinees over the infected controls on all post challenge days and was found that maximum protection was provided by 78 kDa + rIL-12 vaccine and it was highly immunogenic as depicted by the reduction in parasite load (71–94.8%), reduction in infection rate of peritoneal macrophages (92.9–98%), enhanced DTH response (6.5–10.5 fold), increase in IgG2a anti-leishmanial antibody production (3–3.7 fold) and up-regulation of IFN-γ (3.7–6.5 fold) and IL-2 levels (7.7–12.3 fold), which demonstrate the generation of protective Th1 type of immune response. Comparable results were also observed in 78 kDa + MPL-A and liposome-encapsulated 78 kDa vaccines with 56.5–92% and 62.9–93.4% reduction in parasite load respectively. Significant results have also been obtained with 78 kDa antigen + ALD, 78 kDa antigen + FCA and 78 kDa antigen alone group but the protective efficacy was reduced as compared to the other vaccine groups. The present study indicates that the three vaccine formulations i.e. 78 kDa antigen + rIL-12, liposome-encapsulated 78 kDa antigen and 78 kDa antigen + MPL-A, are highly efficacious and effective vaccine candidates against visceral leishmaniasis.