Assessment of Protection Induced by DNA and Live Vaccine Encoding Leishmania MHC Class I Restricted Epitopes against L. major Challenge in Balb/c Mice Model

Zandieh, Mojgan; Kashi, Tahereh; Taheri, Tahereh

doi:10.4172/1948-5948.1000250

Cited by 11 publications

(9 citation statements)

References 59 publications

(69 reference statements)

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“…Interestingly, the predicted antigenicity of fatty acid elongase (XP_003859440.1) was less than the threshold value. But previous reports demonstrated an enhanced IFN-g production against the peptide derived from L. major fatty acid elongase [Lee and Geraghty, 1996;Herrera-Najera et al, 2009;Zandieh et al, 2015]. Thus, fatty acid elongase was included in the further study.…”

Section: Screening Of L Donovani Genome For Identification and Charamentioning

confidence: 99%

Mining the Proteome of Leishmania donovani for the Development of Novel MHC Class I Restricted Epitope for the Control of Visceral Leishmaniasis

Dikhit

Vijayamahantesh

Kumar

et al. 2017

J of Cellular Biochemistry

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Although, the precise host defence mechanism(s) is not completely understood, T cell-mediated immune responses is believed to play a pivotal role in controlling parasite infection. Here we target the stage dependent over expressed gene. Here, the consensus based computational approach was adopted for the screening of potential major histocompatibility complex class I restricted epitopes. Based on the computational analysis and previously published report, a set 19 antigenic proteins derived from Leishmania donovani were screened for further characterization as vaccine candidates. A total of 49 epitopes were predicted, which revealed a comprehensive binding affinity to the 40 different MHC class I supertypes. Based on the population coverage and HLA cross presentation, nine highly promiscuous epitopes such as LTYDDVWTV (P1), FLFPQRTAL(P2), FLFSNGAVV (P3), YIYNFGIRV (P4), YMTAAFAAL (P5), KLLRPFAPL (P6), FMLGWIVTI (P7), SLFERNKRV (P8), and SVWNRIFTL (P9) which have either a high or an intermediate TAP binding affinity were selected for further analysis. Theoretical population coverage analysis of polytope vaccine (P1-P9) revealed more than 92% population. Stimulation with the cocktail of peptide revealed a proliferative CD8 þ T cell response and increased IFN-g production. An upregulated NFkB activity is thought to be play a pivotal role in T cell proliferation against the selected peptide. The Th1-type cytokine profile (presence of IFN-g and absence of IL-10) suggests the potentiality of the cocktail of epitope as a subunit vaccine against leishmaniasis. However, the efficiency of these epitopes to trigger other Th1 cytokines and chemokines in a humanized mice model could explore its plausibility as a vaccine candidate.

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Section: Screening Of L Donovani Genome For Identification and Charamentioning

confidence: 99%

Mining the Proteome of Leishmania donovani for the Development of Novel MHC Class I Restricted Epitope for the Control of Visceral Leishmaniasis

Dikhit

Vijayamahantesh

Kumar

et al. 2017

J of Cellular Biochemistry

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“…Leishmaniasis is as an important neglected tropical disease in poverty-stricken countries of Africa, South America, and Asia [ 1 , 2 ]. Leishmaniasis has three major manifestations: Visceral leishmaniasis, cutaneous leishmaniasis and mucocutaneous leishmaniasis [ 3 ]. Considering the complex life cycle including promastigote (as an extracellular flagellated form) and amastigote (as an intracellular aflagellated form) with differential protein expression, parasite elimination is a hard task and controlling the disease is difficult [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Human Neutrophil Peptide 1 as immunotherapeutic agent against Leishmania infected BALB/c mice

et al. 2017

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Human Neutrophil Peptide 1 (HNP1) produced by neutrophils, is a well-known antimicrobial peptide which plays a role both in innate as well as in adaptive immunity and is under intensive investigation as a potential therapeutic agent. Previous in vitro experiments have indicated the leishmaniacidal effect of recombinant HNP1 on Leishmania major (L. major) promastigotes and amastigotes. In the current study, we further extended the idea to explore the remedial effect of HNP1 in the two modalities of peptide therapy (folded HNP1) and gene therapy in L. major infected BALB/c mice. To this end, mice in five different groups received synthetic folded HNP1 (G1), pcDNA-HNP1-EGFP (G2), pcDNA-EGFP (G3), Amphotericin B (G4) and PBS (G5), which was started three weeks after infection for three consecutive weeks. Footpad swelling was monitored weekly and a day after the therapy ended, IFN-γ, IL-4, IL-10, IL-6 and nitric oxide produced by splenocytes were analyzed together with the parasite load in draining lymph nodes. Arginase activity and dermal histopathological changes were also analyzed in the infected footpads. We demonstrated that both therapeutic approaches effectively induced Th1 polarization and restricted parasite burden. It can control disease progression in contrast to non-treated groups. However, pcDNA-HNP1-EGFP is more promising in respect to parasite control than folded HNP1, but less effective than AmB treatment. We concluded with the call for a future approach, that is, a DNA-based expression of HNP1 combined with AmB as it can improve the leishmaniacidal efficacy.

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“…Moreover, a reduction in parasite load in the liver and spleen of challenged mice was observed ( 28 ). More recently, with the advance of recombinant DNA technology, DNA sequences for peptides have been used to design DNA vaccines ( 25 , 48 ) or to develop attenuated virus (e.g., adenovirus) or phage display that can translate the peptide sequence and drive strong T-cell responses ( 32 , 45 , 49 ). DNA and adenovirus vaccines (Figure 2 ) have demonstrated to be strong inducers of T-cell activation leading to intracellular parasite control ( 24 , 30 ).…”

Section: Leishmanial Peptide-based Vaccinesmentioning

confidence: 99%

“…DNA and adenovirus vaccines (Figure 2 ) have demonstrated to be strong inducers of T-cell activation leading to intracellular parasite control ( 24 , 30 ). Several studies emphasize that these approaches are the future for peptide vaccine design ( 24 , 25 , 30 , 48 ). For example, Das et al ( 24 ) proposed a polyepitope DNA vaccine that showed promising results in mice.…”

Section: Leishmanial Peptide-based Vaccinesmentioning

confidence: 99%

Peptide Vaccines for Leishmaniasis

et al. 2018

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Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

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Assessment of Protection Induced by DNA and Live Vaccine Encoding Leishmania MHC Class I Restricted Epitopes against L. major Challenge in Balb/c Mice Model

Cited by 11 publications

References 59 publications

Mining the Proteome of Leishmania donovani for the Development of Novel MHC Class I Restricted Epitope for the Control of Visceral Leishmaniasis

Mining the Proteome of Leishmania donovani for the Development of Novel MHC Class I Restricted Epitope for the Control of Visceral Leishmaniasis

Human Neutrophil Peptide 1 as immunotherapeutic agent against Leishmania infected BALB/c mice

Peptide Vaccines for Leishmaniasis

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