Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

Abstract

BackgroundThe development of an effective vaccine against visceral leishmaniasis (VL) caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg) against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG) and Monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) with cationic liposomes, in combination with LAg, to confer protection against murine VL.ResultsAll the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg.ConclusionThis comparative study reveals greater effectiveness of the liposomal vaccine for protection against progressive VL in BALB/c. Again, evaluation of the immune responses by vaccination emphasizes the need of stimulation of potent cellular immunity based on both Th1 and Th2 cell responses to confer protection against VL.

Selection of Adjuvants for Enhanced Vaccine Potency

“…Liposomes can generate more efficient immune response [180] and less side effect (limited IgE levels) than aluminum-adjuvanted vaccines [171]. Greater effectiveness was observed in mice for a leishmaniasis vaccine adjuvanted with cationic liposomes than those adjuvanted with BCG or MPL plus trehalose dicorynomycolate [178]. Vaxfectin, a cationic lipid-based adjuvant, was shown to increase the immune response for a seasonal influenza vaccine with a  10-fold dose sparing effect in mice and the type of effect (Th1 or Th2) could be directed simply by varying the ratio of adjuvant to antigen [181,182].…”

“…Liposomes can induce different types and levels of immune response for a variety of vaccines/antigens, such as cytosolic proteins (sAg) of Plasmodium yoelii nigeriensis [170], tuberculosis vaccine candidate Ag85B-ESAT-6 [176], flu vaccine [169,177], leishmanial antigen vaccine [178], and DNA vaccine [179]. Liposomes can generate more efficient immune response [180] and less side effect (limited IgE levels) than aluminum-adjuvanted vaccines [171].…”

The effect of chitosan nanospheres on the immunogenicity of Toxoplasma lysate vaccine in mice

“…BCNS were prepared according to the method of DaneshBahreinni et al (2011) and Ravindran et al (2010) using ionotropic gelation process. Both chitosan (deacetylation C85 %; Sigma) and tripolyphosphate pentabasic (TPP) powder (Sigma-Aldrich) were used in the preparation of the nanospheres.…”

Molecular Cloning of Leishmania major gp63 Gene in BALB/c Mouse CT26 Cell Line

“…Different attempts have been made to generate Leishmania vaccines using recombinant immunogenic Leishmania proteins expressed in microbial vectors but none has yet been introduced as a vaccine for Leishmania [18,19]. However, the potency of mammalian cells in expression of Leishmania immunogenic genes is not yet fully cleared.…”