Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.
Leishmaniasis is a neglected tropical disease caused by Leishmania species. It is a major health concern affecting 88 countries and threatening 350 million people globally. Unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. The emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. The genome sequence of Leishmania, provides access to novel genes that hold potential as chemotherapeutic targets or vaccine candidates. In this study, we selected 19 antigenic genes from about 8000 common Leishmania genes based on the Leishmania major and Leishmania infantum genome information available in the pathogen databases. Potential vaccine candidates thus identified were screened using an in vitro high throughput immunological platform developed in the laboratory. Four candidate genes coding for tuzin, flagellar glycoprotein-like protein (FGP), phospholipase A1-like protein (PLA1) and potassium voltage-gated channel protein (K VOLT) showed a predominant protective Th1 response over disease exacerbating Th2. We report the immunogenic properties and protective efficacy of one of the four antigens, tuzin, as a DNA vaccine against Leishmania donovani challenge. Our results show that administration of tuzin DNA protected BALB/c mice against L. donovani challenge and that protective immunity was associated with higher levels of IFN-γ and IL-12 production in comparison to IL-4 and IL-10. Our study presents a simple approach to rapidly identify potential vaccine candidates using the exhaustive information stored in the genome and an in vitro high-throughput immunological platform.
['Lakshmi|Bhavana Sethu|BS|', 'Wang|Ruobing|R|', 'Madhubala|Rentala|R|']
D000818:Animals D000913:Antibodies, Protozoan D030541:Databases, Genetic D005260:Female D018503:Genome, Protozoan D057166:High-Throughput Screening Assays D007074:Immunoglobulin G D007371:Interferon-gamma D016753:Interleukin-10 D018664:Interleukin-12 D015847:Interleukin-4 D007893:Leishmania donovani D054332:Leishmaniasis Vaccines D007898:Leishmaniasis, Visceral D008565:Membrane Proteins D008807:Mice, Inbred BALB C D015800:Protozoan Proteins D018417:Th1 Cells D019444:Vaccines, DNA
Genome Tuzin DNA vaccine Immune response In vitro screening Leishmania vaccine