Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice

Amit, Ajay; Vijayamahantesh,; Dikhit, Manas Ranjan; Singh, Ashish Kumar; Kumar, Vikash; Suman, Shashi S.; Singh, Ankita; Kumar, Akhilesh; Thakur, Ajit Kumar; Das, Vidyanand Ravi; Das, Pradeep; Bimal, Sanjiva

doi:10.1016/j.molimm.2016.12.022

Cited by 42 publications

(23 citation statements)

References 62 publications

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“…Leishmania membrane and extracellular proteins may be related to parasite immune escape, so the application of intracellular proteins, especially some enzymes, as vaccines has been studied often and has shown good immune effects . This study represents the first use of CaNA2 as a vaccine in VL experiments.…”

Section: Discussionmentioning

confidence: 99%

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

Fan²,

Zhang

et al. 2018

Immunology

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Summary Visceral leishmaniasis is a tropical and neglected disease with an estimated 200 000–400 000 cases and 60 000 deaths worldwide each year. Currently, no clinically valid vaccine is available for this disease. In this study, we formulated DNA and protein vaccines encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis. We predicted the secondary and tertiary structures, surface properties, subcellular localization, potential binding sites and HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2. The best candidate CpG ODN (2395, M362, D‐SL03 or 685) was screened out as a DNA vaccine adjuvant. We also prepared Kmp‐11 and Kmp‐11/CaNA2 DNA and protein vaccines, respectively, for comparison. BALB/c mice were immunized with a DNA prime‐protein boost immunization strategy and challenged with a newly isolated Leishmania strain from an individual with visceral leishmaniasis. The IgG antibody titers showed that our vaccine had strong immunogenicity with a long duration, especially cellular immunity. The spleen parasite burden of each group demonstrated that the CaNA2 vaccine had a certain immune protective effect on visceral leishmaniasis in BALB/c mice, and the amastigote reduction rate reached 76%. Preliminary safety tests confirmed the safety of the vaccine. Our work demonstrates that the HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitope CaNA2 DNA prime‐protein boost vaccine may be a safe and effective epitope vaccine candidate against visceral leishmaniasis.

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Section: Discussionmentioning

confidence: 99%

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

Fan²,

Zhang

et al. 2018

Immunology

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“…9 In this regard, many attempts were made to explore the vaccine potential of different Leishmania antigens such as GP-63, KMP-11, protein disulphide isomerase and haemoglobin receptors. [10][11][12][13] However, none of these strategies offer significant protection and are yet to be applied in phase I clinical trial. Our previous studies revealed that ornithine decarboxylase (ODC) derived from Leishmania donovani have the potential to elicit the immune cells by influencing multifunctional CD4 + and CD8 + T cell-mediated activities 14,15 with a robust Th1 immune response and reduced parasite load in spleens.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Evaluating the immunomodulatory responses of LdODC‐derived MHC Class‐II restricted peptides against VL

Pandey

Dikhit

Kumar

et al. 2020

Parasite Immunology

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In a bid to develop a novel immunoprophylactic measure against visceral leishmaniasis (VL), MHC class‐II–restricted epitopes of LdODC were identified by reverse vaccinology approach. Five consensus HLA‐DRB1*0101‐restricted epitopes were screened. The analysis revealed that the set of epitopes was presented by at least 54 diverse MHC class‐II alleles. Based on in silico screening, followed by molecular dynamics simulation, population coverage analysis, and HLA cross‐presentation ability, five best epitopes were evaluated. PBMCs isolated from treated VL subjects, when stimulated with synthetic peptide alone or as a cocktail of peptides, triggered a secretory IFN‐γ, but not the IL‐10 level. Support in this notion came from intracellular cytokine level with a considerable up‐regulated IFN‐γ produced by CD4+ T cells. Also, the enhanced IFN‐γ seemed to be augmented with the activation of macrophages with prominent IL‐12 production. Therefore, it can be concluded that the screened MHC class‐II–restricted epitope hotspots derived from Leishmania ODC can trigger CD4+ T cells, which can skew macrophage functions towards protection. However, a detailed analysis can explore its potentiality as a vaccine candidate.

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“…Various strategies have been employed to date to develop specific antileishmanial vaccines such as killed parasites, live attenuated parasites, subunit vaccines using proteins of different stages of the parasite life cycle and DNA vaccines, dendritic cell‐based vaccines and salivary antigen‐based vaccines . Many of these strategies have resulted in protection of the mouse model.…”

Section: Introductionmentioning

confidence: 99%

Vaccine potential of HLA‐A2 epitopes from Leishmania Cysteine Protease Type III (CPC)

Dikhit

Amit

Singh

et al. 2017

Parasite Immunology

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Although the precise host-defence mechanisms are not completely understood, T-cell-mediated immune responses are believed to play a pivotal role in controlling parasite infection. In this study, the potential HLA*A2 restricted peptides were predicted and the ability of peptides to bind HLA-A*02 was confirmed by a MHC stabilization assay. Two of the peptides tested stabilized HLA-A*02: (a) LLATTVSGL (P1) and (b) LMTNGPLEV (P3). The potential of the peptides to generate protective immune response was evaluated in patients with treated visceral leishmaniasis as well as in healthy control subjects. Our data suggest that CD8 T-cell proliferation against the selected peptide was significantly higher compared to unstimulated culture conditions. The stimulation of peripheral blood mononuclear cells with epitopes individually or as a cocktail upregulated IFN-γ production, which indicates its pivotal role in protective immune response. The IFN-γ production was mainly in a CD8 T-cells-dependent manner, which suggested that these epitopes had an immunoprophylactic potential in a MHC class I-dependent manner. Moreover, no role of the CD3 T cell was observed in the IL-10 production against the selected peptides, and no role was found in disease pathogenesis. Further studies on the role of these synthetic peptides may contribute significantly to developing a polytope vaccine idea towards leishmaniasis.

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Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice

Cited by 42 publications

References 62 publications

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

Retracted: Evaluating the immunomodulatory responses of LdODC‐derived MHC Class‐II restricted peptides against VL

Vaccine potential of HLA‐A2 epitopes from Leishmania Cysteine Protease Type III (CPC)

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