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.
Highlights
The development of an effective vaccine against visceral leishmaniasis (VL) caused by Leishmania donovani is an essential aim for controlling the disease
In the present study the protective efficacy of L. donovani promastigote antigens (LAg) with Bacille Calmette-Guerin (BCG) and Monophosphoryl lipid A (MPL)-trehalose dicorynomycolate (TDM) were evaluated and compared with LAg entrapped in cationic liposomes when given by same intraperitoneal route against experimental challenge of L. donovani in BALB/c mice
Comparison of parasite burden in differently adjuvanted LAg vaccinated mice after L. donovani challenge infection To compare the efficacy of vaccination against VL with LAg in three different adjuvants, BALB/c mice were immunized intraperitoneally with BCG + LAg, MPLTDM+LAg and LAg entrapped in cationic liposomes
Summary
The development of an effective vaccine against visceral leishmaniasis (VL) caused by Leishmania donovani is an essential aim for controlling the disease. Bacille Calmette-Guerin (BCG) and Monophosphoryl lipid A (MPL) are two immunostimulatory adjuvants that act directly on the immune system to augment cell-mediated response to the associated antigens. MPL, the non-toxic derivative of the lipopolysaccharide (LPS) of Salmonella minnesota is a safe and well-tolerated adjuvant approved for human use It signals via TLR4 for the activation of T-cell effector response. Cationic liposomes are lipid-bilayer vesicles with a positive surface charge that have emerged as a promising new adjuvant technology having low toxicity and biodegradability. They are very effective antigen-deliver systems and serve to markedly enhance the uptake and presentation of antigens by antigen presenting cells. They potentiate cell-mediated and humoral immune response to poorly immunogenic protein and peptide antigens [11,12,13,14] and generate solid and durable immunity against experimental VL [15,16,17,18]
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