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A randomized double-blind Phase IIb trial to evaluate the efficacy of ChAd63-KH for the treatment of post kala-azar dermal leishmaniasis

ABSTRACT: A randomized double-blind Phase IIb trial to evaluate the efficacy of ChAd63-KH for the treatment of post kala-azar dermal leishmaniasis

PROVIDER: PRJNA1106492 | ENA |

REPOSITORIES: ENA

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A Proteomic map of Leishmania donovani isolate from post kala-azar dermal leishmaniasis (PKDL) patient

Project description:In the present study, we carried out in-depth proteomic analysis of a clinical isolate of post kala-azar dermal leishmaniasis (PKDL) L. donovani promastigotes. The high-resolution mass spectrometry data was searched against protein database of L. donovani. This resulted in identification of 5, 283 unique proteins in L. donovani accounting for 61% of L. donovani proteome. This is one of the most in-depth proteome profile of L. donovani as well as across the different Leishmania species analyzed till date.

2022-03-13 | PXD020541 | Pride

A randomized double-blind Phase IIb trial to evaluate the efficacy of ChAd63-KH for the treatment of post kala-azar dermal leishmaniasis

Project description:Purpose: The goals of this study were to identify molecular patterns activated by the vaccine and potential predictors of clinical success.

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Expression profiling of Sudanese visceral leishmaniasis patients pre- and post-treatment with sodium stibogluconate

Project description:Visceral leishmaniasis (VL) in Sudan caused by Leishmania donovani is fatal in susceptible individuals if untreated. Treatment with Sodium Stibogluconate (SSG) leads to post kala azar dermal leishmaniasis (PKDL) in 58% of patients. Here Affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (N=9 paired samples) pre- and post-treatment with SSG. Using the Bioconductor package limma, 438 genes from 28,869 post quality-control probe-sets were differentially expressed (Pnominal≤0.02) post- versus pre-treatment. Canonical pathway analysis using Ingenuity Pathway Analysis identified “Role of NFAT in Regulation of Immune Response” (Pnominal=1.35x10-5; PBH-adjusted=4.79x10-3), “B Cell Development” (Pnominal=2.04x10-4; PBH-adjusted=0.024), “Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes” (Pnominal=2.04x10-4; PBH-adjusted=0.024), and “OX40 Signaling” (Pnominal=2.82x10-4; PBH-adjusted=0.025) as pathways differentially regulated post- versus pre-treatment. Major network hub genes included TP53, FN1, MYC, BCL2, JUN, SYK, RUNX2, MMP1 and ACTA2. Top endogenous upstream regulators included IL-7 (P=2.28x10-6), TNF (P=4.26x10-6), APP (P=4.23x10-5) and SPI1/PI.1 (P=1.17x10-7). Top predicted chemical drug regulators included the flavonoid genistein (P=4.56x10-7) and the quinoline alkaloid camptothecin (P=5.14x10-5). These results contribute to our understanding of immuno-pathology associated with VL and response to SSG treatment. Further replication could identify novel therapeutic strategies that improve on SSG treatment and reduce the likelihood of progression to PKDL.

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A chimpanzee adenovirus-vectored single dose therapeutic vaccine for post kala azar dermal leishmaniasis

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Project description:Leishmania donovani isolated from patients of Post kala azar derml Leishmaniasis (PKDL).

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Project description:The debilitating disease kala-azar or visceral leishmaniasis (VL) is caused by the kinetoplastid protozoan parasite Leishmania donovani. The parasite is transmitted by the hematophagous sandfly vector of the genus Phlebotomus in the old world and Lutzomyia in the new world. The predominant Phlebotomine species associated with transmission of kala-azar are Phlebotomus papatasi and Phlebotomus argentipes. The infected female sandfly transmits the parasite when it takes a blood meal. Understanding the molecular interaction of the sand fly-Leishmania during the development of parasite within the gut of the sandfly is crucial to understanding parasite life cycle. The complete genome sequences of sandfly vectors (Phlebotomus and Lutzomyia) are currently not available and sequencing efforts are underway. Non-availability of genome sequence can hamper identification of proteins in the sandfly vector. In the present study we have carried out proteogenomic analysis of unsequenced sandfly vector P. paptasi cell line using high-resolution mass spectrometry and comparative homology-based searches using related dipteran protein data (mosquitoes and fruit fly). This study resulted in identification of 1,312 proteins from P. papatasi based on homology. Our study demonstrates the power of proteogenomic approaches in mapping the proteomes of unsequenced organisms.

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Project description:Genome wide comparison of Leishmania donovani strains from Indian visceral leishmaniasis and para-kala-azar dermal leishmaniasis patients

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