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

Kaur, Tejinder; Thakur, Ajay D.; Kaur, Sukhbir

doi:10.1007/s12639-012-0171-7

Cited by 10 publications

(6 citation statements)

References 48 publications

(52 reference statements)

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“…For the evaluation of cytokine levels, cell suspensions from spleen of normal controls, infected controls and immunized mice were prepared and cultured in 96-well plates in RPMI-1640 containing 20 mM NaHCO 3 , 10 mM HEPES, 10 U/ml of penicillin, 100 µg/ml streptomycin and 2 mM l-glutamine and 10 % FCS. Cells were stimulated with 50 μg/ml of crude antigen of L. donovani [29]. Cells were incubated at 37 °C in a humified chamber containing 5 % CO 2 for 72 h and supernatants were collected and stored at −20 °C [30].…”

Section: × Weight Of Organ In Milligramsmentioning

confidence: 99%

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

Thakur

Kaur

2014

Med Microbiol Immunol

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Visceral leishmaniasis (VL) caused by Leishmania donovani is a life-threatening disease involving uncontrolled parasitization of vital organs. Drugs to treat leishmaniasis have one or more limitations or insufficiencies in the long run. A safe and efficacious vaccine to control this disease is needed. Killed antigens that could be safer as vaccines have shown limited efficacy in clinical trials. Immunogenic enhancement with appropriate adjuvants may thus be required to elicit protective immunity based on antibodies and effector T-cell functions. Therefore, it is essential to search for adjuvant to enhance the immunogenicity of killed vaccines and to induce protection against leishmaniasis. So, the aim of the present study was to compare the effectiveness of four adjuvants, i.e. alum, saponin, monophosphoryl lipid A, cationic liposome in combination with Killed Leishmania donovani (KLD) antigen against murine VL. Animals were immunized subcutaneously thrice at an interval of 2 weeks with a final volume of 100 μl per dose. Challenge infection was given 2 weeks after last booster. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post-infection/challenge days. The protective efficacy of vaccines was revealed by significant reduction in parasite burden and enhanced DTH responses in comparison with the infected controls. Immunized animals also generated significant levels of Th1 cytokines and increased production of IgG2a, thus indicating the generation of a protective Th1 response. All the adjuvants imparted significant protection, but liposomal formulation was most effective followed by KLD + MPL-A, KLD + saponin, KLD + alum and KLD antigen.

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Section: × Weight Of Organ In Milligramsmentioning

confidence: 99%

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

Thakur

Kaur

2014

Med Microbiol Immunol

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“…We used IgG1 and IgG2 responses as indicators to evaluate tuzin immunogenicity in tuzin-immunized parasite-challenged mice since their response is entirely T-cell-dependent ( 58 ). IgG2a antibodies imply a protective Th1 immune response, whereas IgG1 antibodies indicate a Th2 immune response ( 59 ). It has been noted that Leishmania infection triggers host IgG1, which increases IL-10 secretion which aids in the worsening of the disease ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and protective efficacy of tuzin protein as a vaccine candidate in Leishmania donovani-infected BALB/c mice

Devender,

Sebastian,

Maurya

et al. 2024

Front. Immunol.

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Visceral leishmaniasis (VL) is referred to as the most severe and fatal type of leishmaniasis basically caused by Leishmania donovani and L. infantum. The most effective method for preventing the spread of the disease is vaccination. Till today, there is no promising licensed vaccination for human VL. Hence, investigation for vaccines is necessary to enrich the therapeutic repertoire against leishmaniasis. Tuzin is a rare trans-membrane protein that has been reported in Trypanosoma cruzi with unknown function. However, tuzin is not characterized in Leishmania parasites. In this study, we for the first time demonstrated that tuzin protein was expressed in both stages (promastigote and amastigote) of L. donovani parasites. In-silico studies revealed that tuzin has potent antigenic properties. Therefore, we analyzed the immunogenicity of tuzin protein and immune response in BALB/c mice challenged with the L. donovani parasite. We observed that tuzin-vaccinated mice have significantly reduced parasite burden in the spleen and liver compared with the control. The number of granulomas in the liver was also significantly decreased compared with the control groups. We further measured the IgG2a antibody level, a marker of Th1 immune response in VL, which was significantly higher in the serum of immunized mice when compared with the control. Splenocytes stimulated with soluble Leishmania antigen (SLA) displayed a significant increase in NO and ROS levels compared with the control groups. Tuzin-immunized and parasite-challenged mice exhibit a notable rise in the IFN-γ/IL-10 ratio by significantly suppressing IL-10 expression level, an immunosuppressive cytokine that inhibits leishmanicidal immune function and encourages disease progression. In conclusion, tuzin immunizations substantially increase the protective immune response in L. donovani-challenged mice groups compared with control.

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“…However, saponins show some toxicity towards mammals, and their use is not generally authorized for humans, except for more purified and expensive fractions [ 47 ]. MPLA has been shown to stimulate a polarized Th1-type immune response in immunized mice, with the concomitant production of IL-2, TNF-α and IFN-γ cytokines and expression of costimulatory molecules [ 48 , 49 ]. MPLA is a clinically proven adjuvant for humans with low toxicity and the ability to efficiently stimulate T-cell-mediated immune responses, making it an appropriate candidate for use in vaccines against intracellular pathogens such as Leishmania [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection

et al. 2022

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Currently, there is no licensed vaccine to protect against human visceral leishmaniasis (VL), a potentially fatal disease caused by infection with Leishmania parasites. In the current study, a recombinant chimeric protein ChimT was developed based on T-cell epitopes identified from the immunogenic Leishmania amastigote proteins LiHyp1, LiHyV, LiHyC and LiHyG. ChimT was associated with the adjuvants saponin (Sap) or monophosphoryl lipid A (MPLA) and used to immunize mice, and their immunogenicity and protective efficacy were evaluated. Both ChimT/Sap and ChimT/MPLA induced the development of a specific Th1-type immune response, with significantly high levels of IFN-γ, IL-2, IL-12, TNF-α and GM-CSF cytokines produced by CD4+ and CD8+ T cell subtypes (p < 0.05), with correspondingly low production of anti-leishmanial IL-4 and IL-10 cytokines. Significantly increased (p < 0.05) levels of nitrite, a proxy for nitric oxide, and IFN-γ expression (p < 0.05) were detected in stimulated spleen cell cultures from immunized and infected mice, as was significant production of parasite-specific IgG2a isotype antibodies. Significant reductions in the parasite load in the internal organs of the immunized and infected mice (p < 0.05) were quantified with a limiting dilution technique and quantitative PCR and correlated with the immunological findings. ChimT/MPLA showed marginally superior immunogenicity than ChimT/Sap, and although this was not statistically significant (p > 0.05), ChimT/MPLA was preferred since ChimT/Sap induced transient edema in the inoculation site. ChimT also induced high IFN-γ and low IL-10 levels from human PBMCs isolated from healthy individuals and from VL-treated patients. In conclusion, the experimental T-cell multi-epitope amastigote stage Leishmania vaccine administered with adjuvants appears to be a promising vaccine candidate to protect against VL.

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

Cited by 10 publications

References 48 publications

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

Immunogenicity and protective efficacy of tuzin protein as a vaccine candidate in Leishmania donovani-infected BALB/c mice

A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection

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