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Leishmania Vaccine

Luan Tales Costa de Paiva Vasconcelos, Marcos Antônio Oliveira Filho, Vitor Troccoli Ribeiro, Jaciara Silva de Araújo, Francisco Canindé de Sousa Junior, Daniella Regina Arantes Martins, Everaldo Silvino Dos Santos
Leishmaniosis is a complex of diseases that can be fatal, if not given proper attention. Despite its relevance in the public health system, there is no vaccine capable of preventing the disease in humans so far and its treatment is expensive and aggressive to human health. The present study aims to optimize the induction parameters of the 503 Leishmania i. chagasi antigen expressed in recombinant Escherichia coli M15. The induction at different cell densities was evaluated in order to analyze the influence of the induction time on the yield of the protein of interest...
November 29, 2018: Preparative Biochemistry & Biotechnology
Thouraya Boussoffara, Sadok Chelif, Melika Ben Ahmed, Mourad Mokni, Afif Ben Salah, Koussay Dellagi, Hechmi Louzir
Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major infection is characterized by different clinical presentations which depend in part on the host factors. In attempt to investigate the impact of the host's immune response in the outcome of the disease, we conducted a prospective study of 453 individuals living in endemic foci of L. major transmission in Central Tunisia. Several factors were assessed at the baseline including (i) the presence of typical scars of ZCL, (ii) in vivo hypersensitivity reaction to leishmanin, and (iii) the in vitro release of granzyme B (Grz B) by peripheral blood mononuclear cells (PBMC) in response to stimulation with live L...
2018: Frontiers in Cellular and Infection Microbiology
Mohd Imran Khan, Anshul Mishra, Pravin K Jha, Kumar Abhishek, Rachna Chaba, Pradeep Das, Kislay K Sinha
The visceral leishmaniasis is caused by L. donovani, a neglected tropical disease with an estimated number of 500,000 cases worldwide. Apart from the absence of effective vaccine, the available drugs have limitations like toxic side effects and emergence of drug resistance. The genome of Leishmania is remarkably challenged by the oxidative stress present inside the human macrophage. To maintain genomic integrity, a number of specialized DNA repair pathways assist in the recognition and repair of damaged DNA...
November 16, 2018: International Journal of Biological Macromolecules
J Risueño, T Spitzová, L J Bernal, C Muñoz, M C López, M C Thomas, J J Infante, P Volf, E Berriatua
A 2-year longitudinal study of enzyme-linked immunosorbent assay (ELISA) antibodies against Phlebotomus perniciosus and Phlebotomus papatasi (Diptera: Psychodidae) sandfly saliva was performed in 32 Beagle dogs treated preventively with an imidacloprid-permethrin topical insecticide in an endemic area in Spain. Dogs were grouped into three sandfly exposure groups according to the time of inclusion in the study. Assays analysed immunoglobulin G (IgG) against salivary gland homogenates (SGH) of both species and recombinant P...
November 18, 2018: Medical and Veterinary Entomology
Patrick Lypaczewski, Johanna Hoshizaki, Wen-Wei Zhang, Laura-Isobel McCall, John Torcivia-Rodriguez, Vahan Simonyan, Amanpreet Kaur, Ken Dewar, Greg Matlashewski
Leishmania donovani is responsible for visceral leishmaniasis, a neglected and lethal parasitic disease with limited treatment options and no vaccine. The study of L. donovani has been hindered by the lack of a high-quality reference genome and this can impact experimental outcomes including the identification of virulence genes, drug targets and vaccine development. We therefore generated a complete genome assembly by deep sequencing using a combination of second generation (Illumina) and third generation (PacBio) sequencing technologies...
November 8, 2018: Scientific Reports
Razieh Tavakoli Oliaee, Iraj Sharifi, Ali Afgar, Abdollah Jafarzadeh, Amir Tavakoli Kareshk, Mehdi Bamorovat, Hamid Sharifi, Zahra Babaei, Alireza Keyhani, Leili Abedi, Amir Keyhani, Fatemeh Sharifi
BACKGROUND: Detection of the mechanism of host/parasite interactions in unresponsive forms of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica is helpful for immunotherapy and vaccine development. In the present study, the gene expression of toll-like receptors (TLRs), TNF-α, iNOS and also arginase (ARG) activity in monocytes from Glucantime unresponsive in comparison to responsive patients infected with L. tropica was investigated. METHODS: In this case-control study, patients with unresponsive (n = 10) and responsive (n = 10) ACL were recruited...
November 3, 2018: Microbial Pathogenesis
Malcolm S Duthie, Neal Van Hoeven, Zachary MacMillen, Alessandro Picone, Raodoh Mohamath, Jesse Erasmus, Fan-Chi Hsu, Dan T Stinchcomb, Steven G Reed
The rapid generation of strong T cell responses is highly desirable and viral vectors can have potent CD8+ T cell-inducing activity. Immunity to leishmaniasis requires selective T cell responses, with immunization schemes that raise either CD4 or CD8 T cell responses being protective in small animal models. We have defined the leishmaniasis vaccine candidate recombinant fusion antigens, LEISH-F2 and LEISH-F3+, that when formulated in a stable emulsion with a Toll-like receptor (TLR) 4 agonist, induce protective CD4+ T cell responses in animal models as well as providing therapeutic efficacy in canine leishmaniasis and in clinical trials in leishmaniasis patients...
2018: Frontiers in Immunology
Behrokh Farahmand, Najmeh Taheri, Hadiseh Shokouhi, Hoorieh Soleimanjahi, Fatemeh Fotouhi
The 23-amino acid ectodomain of influenza virus M2 protein (M2e) is highly conserved among human influenza virus variants and represents an attractive target for developing a universal vaccine. Although this peptide has limited potency and low immunogenicity, the degree of M2e density has been shown to be a critical factor influencing the magnitude of epitope-specific responses. The aim of this study was to design a chimer protein consisting of three tandem repeats of M2e peptide sequence fused to the Leishmania major HSP70 gene and evaluate its characteristics and immunogenicity...
October 31, 2018: Virus Genes
Aditi Shah, Souvik Sen Gupta
Leishmaniasis is a dreaded disease caused by protozoan parasites belonging to the genus Leishmania which results in significant morbidity and mortality worldwide. There are no vaccines available currently for the treatment of Leishmaniasis and chemotherapy still remains the mainstay for anti-leishmanial therapeutics. However, toxicity, reduced bioavailability, high cost and chemoresistance are the principal problems which limit the use of the available drugs. In this context, anti-leishmanial nanotherapeutics may show the way for effective treatment of this dreaded disease...
October 22, 2018: Current Drug Metabolism
Alejandro Llanes, Carlos Mario Restrepo, Ricardo Lleonart
Leishmania is a protozoan parasite causing several disease presentations collectively known as leishmaniasis. Pathogenic species of Leishmania are divided into two subgenera, L. (Leishmania) and L. (Viannia). Species belonging to the Viannia subgenus have only been reported in Central and South America. These species predominantly cause cutaneous leishmaniasis, but in some cases, parasites can migrate to the nasopharyngeal area and cause a highly disfiguring mucocutaneous presentation. Despite intensive efforts, no effective antileishmanial vaccine is available for use in humans, although a few candidates mainly designed for L...
January 1, 2018: Database: the Journal of Biological Databases and Curation
Monique Paiva Campos, Fabiano Borges Figueiredo, Fernanda Nazaré Morgado, Alinne Rangel Dos Santos Renzetti, Sara Maria Marques de Souza, Sandro Antônio Pereira, Rodrigo Nunes Rodrigues-Da-Silva, Josué Da Costa Lima-Junior, Paula Mello De Luca
[This corrects the article DOI: 10.3389/fimmu.2018.01690.].
2018: Frontiers in Immunology
Adnan A Bekhit, Eman El-Agroudy, Aliaa Helmy, Tamer M Ibrahim, Amin Shavandi, Alaa El-Din A Bekhit
Leishmaniasis affects over 150 million people all over the world, especially in subtropical regions. Currently used antileishmanial synthesized drugs are associated with some drawbacks such as resistance and cytotoxicity, which hamper the chances of treatment. Furthermore, effective leishmanial vaccines are not well developed. Promising chemotherapy, either from natural or synthetic compounds, was or still is the most promising treatment. This review focuses on recent findings in drugs used for the treatment of leishmaniasis including; chemical and natural antileishmanial moieties, different potential targets, as well as various trials of vaccination development...
December 5, 2018: European Journal of Medicinal Chemistry
Touraj Miandoabi, Fariborz Bahrami, Vahideh Moein Vaziri, Soheila Ajdary
Background: Cutaneous leishmaniasis (CL) is a serious public health problem in many tropical countries. The infection is caused by a protozoan parasite of Leishmania genus transmitted by Phlebotominae sandflies. In the present study, we constructed a eukaryotic expression vector to produce a fusion protein containing LmSTI1 from Leishmania major (L. major) and PpSP42 from Phlebotomus papatasi (Ph. papatasi) . In future studies we will test this construct as a DNA vaccine against zoonotic CL...
October 2018: Reports of Biochemistry & Molecular Biology
Satish Chandra Pandey, Anubhuti Jha, Awanish Kumar, Mukesh Samant
Visceral leishmaniasis (VL) is one of the most devastating diseases of the tropical region caused by protozoan parasite Leishmania donovani. So far, there is no effective drug and vaccine available against this fatal disease. The DEAD-box RNA helicase is quite essential for the RNA processing, amastigote differentiation and infectivity in Leishmania. In this study, L. donovani DEAD-box RNA helicase (LdHel-67) was evaluated as a potential drug target against VL. Using in-silico approach we have identified ligands that can specifically bind to this protein by using various application of Schrodinger (Maestro, version 10...
January 2019: International Journal of Biological Macromolecules
Abhishek Subramanian, Ram Rup Sarkar
The hurdles in drug and vaccine development pipelines for leishmaniasis, a complex, multifaceted disease, are largely due to the digenetic lifecycle, differential clinical manifestations of the parasite, and the incomplete understanding of its adaptations within its hosts. Here, we discuss the distinct computational and experimental techniques employed to identify the species and stage-specific adaptive mechanisms at different levels of biological organization, the progress made so far, and limitations in comprehending leishmaniasis as a systems biology disease...
December 2018: Trends in Parasitology
Jinlei He, Fan Huang, Jianhui Zhang, Han Chen, Qiwei Chen, Junrong Zhang, Jiao Li, Zhiwan Zheng, Dali Chen, Jianping Chen
Visceral leishmaniasis is a tropical and neglected disease with an estimated 200 000-400 000 cases and 60 000 deaths worldwide each year. Currently, no clinically valid vaccine is available for this disease. In this study, we formulated DNA and protein vaccines encoding HLA-A2, HLA-A24 and HLA-DR1 restricted epitopes of CaNA2 against visceral leishmaniasis. We predicted the secondary and tertiary structures, surface properties, subcellular localization, potential binding sites and HLA-A2, HLA-A24 and HLA-DR1 restricted epitopes of CaNA2...
October 4, 2018: Immunology
Beatriz C S Salles, Daniel S Dias, Bethina T Steiner, Daniela P Lage, Fernanda F Ramos, Patrícia A F Ribeiro, Thaís T O Santos, Mariana P Lima, Lourena E Costa, Ana T Chaves, Miguel A Chávez-Fumagalli, Ricardo T Fujiwaraa, Lílian L Buenoa, Rachel B Caligiorne, Danielle F de Magalhães-Soares, Julia A G Silveira, Ricardo A Machado-de-Ávila, Denise U Gonçalves, Eduardo A F Coelho
Serological tests are important tools for the diagnosis of Leishmania infection. However, they are not effective markers to diagnose asymptomatic cases of visceral leishmaniasis (VL) and patients developing tegumentary leishmaniasis (TL), since antileishmanial antibodies can be encountered in low levels resulting in false-negative results in the serological trials. In this context, antigens able to be recognized by antibodies in sera from both VL and TL patients will be desirable to be employed in a more sensitivity and specific diagnosis of disease...
September 21, 2018: Immunobiology
Mosayeb Rostamian, Fariborz Bahrami, Hamid M Niknam
One strategy to control leishmaniasis is vaccination with potent antigens alongside suitable adjuvants. The use of toll-like receptor (TLR) agonists as adjuvants is a promising approach in Leishmania vaccine research. Leishmania (L.) tropica is among the less-investigated Leishmania species and a causative agent of cutaneous and sometimes visceral leishmaniasis with no approved vaccine against it. In the present study, we assessed the adjuvant effects of a TLR4 agonist, monophosphoryl lipid A (MPL) and a TLR7/8 agonist, R848 beside two different types of Leishmania vaccine candidates; namely, whole-cell soluble L...
2018: PloS One
Angela Toepp, Mandy Larson, Geneva Wilson, Tara Grinnage-Pulley, Carolyne Bennett, Adam Leal-Lima, Bryan Anderson, Molly Parrish, Michael Anderson, Hailie Fowler, Jessica Hinman, Eric Kontowicz, Jane Jefferies, Marvin Beeman, Jesse Buch, Jill Saucier, Phyllis Tyrrell, Radhika Gharpure, Caitlin Cotter, Christine Petersen
Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis...
October 15, 2018: Vaccine
Iliano V Coutinho-Abreu, Jesus G Valenzuela
Sand fly salivary proteins that produce a specific antibody response in humans and animal reservoirs have been shown to be promising biomarkers of sand fly exposure. Furthermore, immunity to sand fly salivary proteins were shown to protect rodents and non-human primates against Leishmania infection. We are missing critical information regarding the divergence amongst sand fly salivary proteins from different sand fly vectors, a knowledge that will support the search of broad or specific salivary biomarkers of vector exposure and those for vaccines components against leishmaniasis...
2018: Frontiers in Cellular and Infection Microbiology
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