Evaluation of an immunochemotherapeutic protocol constituted of N-methyl meglumine antimoniate (Glucantime®) and the recombinant Leish-110f®+MPL-SE® vaccine to treat canine visceral leishmaniasis

Abstract

The evaluation of the efficacy of an immunochemotherapy protocol to treat symptomatic dogs naturally infected with Leishmania chagasi was studied. This clinical trial had the purpose to test the combination of N-methyl meglumine antimoniate (Glucantime and the second generation recombinant vaccine Leish-110f plus the adjuvant MPL-SE to treat the canine leishmaniasis (CanL). Thirty symptomatic naturally infected mongrel dogs were divided into five groups. Animals received standard treatment with Glucantime or treatment with Glucantime Leish-110f + MPL-SEas immunochemotherapy protocol. Additional groups received Leish-110f + MPL-SE only, MPL-SE only, or placebo. Evaluation of haematological, biochemical (renal and hepatic function) and plasmatic proteins, immunological (humoral and cellular immune response) and the parasitological test revealed improvement of the clinical parameters and parasitological cure in dogs in both chemotherapy alone and immunochemotherapy cohorts. However, the immunotherapy and immunochemotherapy cohorts had reduced number of deaths, higher survival probability, and specific cellular reactivity to leishmanial antigens, in comparison with chemotherapy cohort only and control groups (adjuvant alone and placebo). These results support the notion of using well-characterized recombinant vaccine as an adjunct to improve the current chemotherapy of CanL.

Protective immunity using MPL-A and autoclaved Leishmania donovani as adjuvants along with a cocktail vaccine in murine model of visceral leishmaniasis

“…The gp63?Hsp70?MPL-A vaccine significantly protected the BALB/c mice against L. donovani infection and reduced the parasite load in liver by 97.13 % and in spleen by 94.35 %. The results are in consistence with previous studies which showed that addition of monophosphoryl lipid plus squalene emulsion (MPL-SE) to a cocktail vaccine (containing H1, HASPB1 and MML) or Leish-110f conferred partial or significant protection in dogs against VL respectively (Moreno et al 2007;Miret et al 2008). Experimental infection of immunized mice and hamsters have demonstrated that Leish-111f?MPL-SE induced significant protection against L. infantum infection, with reduction in parasite loads up to 99.6 % (Coler et al 2007).…”

KSAC, the First Defined Polyprotein Vaccine Candidate for Visceral Leishmaniasis

“…The primary objective of the present study was to develop a subunit vaccine against VL with high efficacy and broad coverage of human or animal populations. Although Leish-111f/L110, our first-generation polyprotein vaccine antigens, are promising, i.e., they are protective against both CL and VL in mouse models (9,11), show therapeutic vaccine efficacy for canine VL (26,45), and are showing some promise in human clinical trials (25,31), the vaccine failed to protect dogs from VL in a field trial (18), and it may be possible to obtain a new construct with improved efficacy. KSAC could be one such antigen, because it consistently protected against L. infantum infection as well as or better than Leish-111f/L110, as shown in this study, and also protected against L. major infection better than L110f using a sandfly challenge model (R. Gomes, C. Teixeira, F. Oliveira, P. G. Lawyer, D.-E. Elnaiem, Y. Goto, A. Bhatia, S. Bertholet, R. N. Coler, R. F. Howard, S. G. Reed, S. Kamhawi, and J. G. Valenzuela, unpublished data).…”

Vaccine candidates for leishmaniasis: A review

“…The mixture of recombinant components of Leish-111f was highly immunogenic in dogs [253] but failed to protect them against L. infantum infection and did not prevent disease development in a phase III trial in dogs [114,254]. Recently, when Leish-110f-MPL-SE was co-administered with Glucantime in dogs, the number of deaths was reduced, there was higher survival probability and specific cellular reactivity upon immunization was observed in comparison to dogs who received Glucantime only [255].…”