Proteomic approaches for discovery of new targets for vaccine and therapeutics against visceral leishmaniasis.

Shraddha Kumari, Awanish Kumar, Mukesh Samant, Shyam Sundar, Neeloo Singh, Anuradha Dube

Division of Parasitology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India.

Journal Article: Proteomics. Clinical applications (impact factor: 1.88). 03/2008; 2(3):372-86. DOI: 10.1002/prca.200780017

Abstract

Visceral leishmaniasis (VL) is the most devastating type caused by Leishmania donovani, Leishmania infantum, and Leishmania chagasi. The therapeutic mainstay is still based on the antiquated pentavalent antimonial against which resistance is now increasing. Unfortunately, due to the digenetic life cycle of parasite, there is significant antigenic diversity. There is an urgent need to develop novel drug/vaccine targets against VL for which the primary goal should be to identify and characterize the structural and functional proteins. Proteomics, being widely employed in the study of Leishmania seems to be a suitable strategy as the availability of annotated sequenced genome of Leishmania major has opened the door for dissection of both protein expression/regulation and function. Advances in clinical proteomic technologies have enable to enhance our mechanistic understanding of virulence/pathogenicity/host-pathogen interactions, drug resistance thereby defining novel therapeutic/vaccine targets. Expression proteomics exploits the differential expression of leishmanial proteins as biomarkers for application towards early diagnosis. Further using immunoproteomics efforts were also focused on evaluating responses to define parasite T-cell epitopes as vaccine/diagnostic targets. This review has highlighted some of the relevant developments in the rapidly emerging field of leishmanial proteomics and focus on its future applications in drug and vaccine discovery against VL.

Source: PubMed

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Keywords

annotated sequenced genome
 
antiquated pentavalent antimonial
 
clinical proteomic technologies
 
define parasite T-cell epitopes
 
differential expression
 
digenetic life cycle
 
functional proteins
 
future applications
 
Leishmania chagasi
 
Leishmania donovani
 
Leishmania infantum
 
Leishmania major
 
leishmanial proteomics
 
novel drug/vaccine targets
 
relevant developments
 
suitable strategy
 
therapeutic mainstay
 
vaccine/diagnostic targets
 
virulence/pathogenicity/host-pathogen interactions
 
Visceral leishmaniasis