Abstract

Visceral leishmaniasis is a neglected infectious disease caused primarily by Leishmania donovani and Leishmania infantum protozoan parasites. A significant number of infections take a fatal course. Drug therapy is available but still costly and parasites resistant to first line drugs are observed. Despite many years of trial no commercial vaccine is available to date. However, development of a cost effective, needle-independent vaccine remains a high priority. Reverse vaccinology has attracted much attention since the term has been coined and the approach tested by Rappuoli and colleagues. This in silico selection of antigens from genomic and proteomic data sets was also adapted to aim at developing an anti-Leishmania vaccine. Here, an analysis of the efforts is attempted and the challenges to be overcome by these endeavors are discussed. Strategies that led to successful identification of antigens will be illustrated. Furthermore, these efforts are viewed in the context of anticipated modes of action of effective anti-Leishmania immune responses to highlight possible advantages and shortcomings.

Highlights

  • A cure or effective prophylaxis for visceral leishmaniasis (VL) known as Kala azar is a prioritized objective in global efforts directed toward improving the situation for people at risk of and patients suffering from Leishmania-infections [1, 2]

  • The KalaNet study reported an estimate of only 1 in 10 infections leading to disease in India and Nepal where more than 50% of globally recorded fatal VL cases occur [10, 11]

  • There is the paradigmatic example of lifelong protection against cutaneous leishmaniasis through the century old practice of Leishmanization

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Summary

Introduction

A cure or effective prophylaxis for visceral leishmaniasis (VL) known as Kala azar is a prioritized objective in global efforts directed toward improving the situation for people at risk of and patients suffering from Leishmania-infections [1, 2]. This in silico selection of antigens from genomic and proteomic data sets was adapted to aim at developing an anti-Leishmania vaccine. Parasite proteins are processed for presentation by proteolysis inside vesicles and it is within a vesicular compartment that peptides form complexes with MHC class I and II histocompatibility antigens [37, 40].

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