title: Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.
abstract: 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.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Bhavana Sethu
authors.initials: BS
authors.lastname: Lakshmi
authors.affiliation: Seattle Biomed, Seattle, WA, United States.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India. Electronic address: madhubala@mail.jnu.ac.in.
authors.forename: Rentala
authors.initials: R
authors.lastname: Madhubala
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D030541:Databases, Genetic; D005260:Female; D018503:Genome, Protozoan; D057166:High-Throughput Screening Assays; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007893:Leishmania donovani; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008565:Membrane Proteins / Q000276:immunology; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: DNA vaccine; Genome; Immune response; In vitro screening; Leishmania vaccine; Tuzin