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Leishmania Vaccine

Raquel Álvarez-Velilla, Maria Del Camino Gutiérrez-Corbo, Carmen Punzón, Maria Yolanda Pérez-Pertejo, Rafael Balaña-Fouce, Manuel Fresno, Rosa María Reguera
BACKGROUND: Visceral leishmaniasis is a neglected parasitic disease with no vaccine available and its pharmacological treatment is reduced to a limited number of unsafe drugs. The scarce readiness of new antileishmanial drugs is even more alarming when relapses appear or the occurrence of hard-to-treat resistant strains is detected. In addition, there is a gap between the initial and late stages of drug development, which greatly delays the selection of leads for subsequent studies. METHODOLOGY/PRINCIPAL FINDINGS: In order to address these issues, we have generated a red-shifted luminescent Leishmania infantum strain that enables long-term monitoring of parasite burden in individual animals with an in vivo limit of detection of 106 intracellular amastigotes 48 h postinfection...
February 14, 2019: PLoS Neglected Tropical Diseases
Hamza Özavcı, Mustafa Kaplan
Background/aim: Thiol-specific antioxidant (TSA) protein is one of the most promising molecules among candidates for vaccine against cutaneous leishmaniasis. It was found to be significantly protective against different Leishmania species. In this study, cloning and molecular characterization of thiol-specific antioxidant gene of L. tropica Turkey isolate (LtTSA) were aimed. Materials and methods: LtTSA was amplified by PCR using the specific primers of TSA gene and cloned into the pcDNA3...
February 11, 2019: Turkish Journal of Medical Sciences
Emilie Giraud, Eline Rouault, Laurence Fiette, Jean-Hervé Colle, Despoina Smirlis, Evie Melanitou
BACKGROUND: Leishmania (L.) spp are intracellular eukaryotic parasites responsible for cutaneous or visceral leishmaniasis, replicating predominantly in macrophages (MF). In C57BL/6 mice virulence with L. amazonensis has been associated with inhibition of Th1 immune responses and an uncontrolled lesion development, whereas DBA/2 mice control any lesion. Parasitic clearance by the MFs requires the activation of proper immune responses. One of the immune related genes expressed in immune cells including MF, codes for osteopontin (OPN)...
February 8, 2019: BMC Microbiology
Germano Castelli, Federica Bruno, Laura Saieva, Riccardo Alessandro, Luca Galluzzi, Aurora Diotallevi, Fabrizio Vitale
In recent years, several studies demonstrated the role of exosomes in intercellular communications, several Leishmania species belonging to subgenera Leishmania and Viannia have been demonstrated to release exosomes, and their role in parasite-macrophage interactions and in leishmaniasis development has been investigated. However, the release of exosomes by Leishmania infantum has not been studied so far. The aim of this study was to isolate and characterize L. infantum exosomes, and to investigate the biological activity of these exosomes in macrophage cultures...
February 1, 2019: Experimental Parasitology
Shokouh Azam Sarrafzadeh, Maryam Nourizadeh, Maryam Mahloojirad, Mohammad Reza Fazlollahi, Raheleh Shokouhi Shoormasti, Mohsen Badalzadeh, Caroline Deswarte, Jean-Laurent Casanova, Zahra Pourpak, Jacinta Bustamante, Mostafa Moin
PURPOSE: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency, triggered by non-tuberculous mycobacteria or Bacillus Calmette-Guérin (BCG) vaccines and characterized by severe diseases. All known genetic etiologies are inborn errors of IFN-γ-mediated immunity. Here, we report the molecular, cellular, and clinical features of patients from 15 Iranian families with disseminated disease without vaccination (2 patients) or following live BCG vaccination (14 patients)...
February 4, 2019: Journal of Clinical Immunology
Mary Marcondes, Michael J Day
Latin America encompasses diverse geographical, cultural and socio-economic conditions, which are reflected in the challenges for infectious disease control in the region. One of the most significant regional infectious diseases for humans and domestic dogs is leishmaniasis, occurring as visceral leishmaniasis (VL) caused by Leishmania infantum (syn. L. chagasi) transmitted by sand flies (Lutzomyia longipalpis) and with a canine reservoir, and the more common cutaneous leishmaniasis (CL) involving multiple Leishmania spp...
January 23, 2019: Research in Veterinary Science
Elham Gholami, Fabiano Oliveira, Tahereh Taheri, Negar Seyed, Safoora Gharibzadeh, Nasim Gholami, Amir Mizbani, Fatemeh Zali, Sima Habibzadeh, Daniel Omid Bakhadj, Claudio Meneses, Kambiz Kamyab-Hesari, Alireza Sadeghipour, Yasaman Taslimi, Fatemeh Khadir, Shaden Kamhawi, Mohammad Ali Mazlomi, Jesus G Valenzuela, Sima Rafati
BACKGROUND: The vector-borne disease leishmaniasis is transmitted to humans by infected female sand flies, which transmits Leishmania parasites together with saliva during blood feeding. In Iran, cutaneous leishmaniasis (CL) is caused by Leishmania (L.) major and L. tropica, and their main vectors are Phlebotomus (Ph.) papatasi and Ph. sergenti, respectively. Previous studies have demonstrated that mice immunized with the salivary gland homogenate (SGH) of Ph. papatasi or subjected to bites from uninfected sand flies are protected against L...
January 11, 2019: PLoS Neglected Tropical Diseases
Patrícia A F Ribeiro, Daniel S Dias, Daniela P Lage, Vívian T Martins, Lourena E Costa, Thaís T O Santos, Fernanda F Ramos, Grasiele S V Tavares, Débora V C Mendonça, Fernanda Ludolf, Dawidson A Gomes, Michele A Rodrigues, Miguel A Chávez-Fumagalli, Eduardo S Silva, Alexsandro S Galdino, Mariana C Duarte, Bruno M Roatt, Daniel Menezes-Souza, Antonio L Teixeira, Eduardo A F Coelho
Vaccination is one the most important strategies for the prevention of visceral leishmaniasis (VL). In the current study, a new Leishmania hypothetical protein, LiHyP, which was previously showed as antigenic in an immunoproteomic search in canine VL, was evaluated regarding its immunogenicity and protective efficacy against Leishmania infantum infection. The effects of the immunization using LiHyP were evaluated when administered as a DNA plasmid (DNA LiHyP) or recombinant protein (rLiHyP) associated with saponin...
February 2019: Molecular Immunology
Mansure Hojatizade, Mahsa Soleymani, Mohsen Tafaghodi, Ali Badiee, Omid Chavoshian, Mahmoud Reza Jaafari
BACKGROUND: Although there have been numerous attempts to develop vaccines for Leishmaniasis, no vaccine can be found against Leishmania in routine use for an effective global vaccination. It seems that one of the reasons for the low efficacy of such vaccines is the lack of a suitable adjuvant. OBJECTIVE: To evaluate the effects of chitosan nanoparticles containing whole Leishmania lysate antigen (WLL) and soluble leishmania antigens (SLA), a first generation Leishmania vaccine, on the type of immune response generated in BALB/c in a murine model of leishmaniasis...
December 2018: Iranian Journal of Immunology: IJI
Jinlei He, Fan Huang, Jiao Li, Qiwei Chen, Dali Chen, Jianping Chen
Visceral leishmaniasis (VL) is a serious and widespread parasitic disease caused by Leishmania donovani complex. The threat of this fatal disease continues due to the lack of ideal drugs or vaccines. In this study, we selected Amastin, CaNA2, Kmp-11 and PDI proteins of Leishmania donovani for study, which are VL vaccine candidates or possible drug targets. Eleven bioinformatics tools were used to analyze different aspects of these proteins, including amino acid composition, topology, signal peptide, secondary structure, surface properties, phosphorylation sites and kinases, protein binding sites, 3D homology modeling, B cell epitopes, MHC class Ⅰ and Ⅱ epitopes and protein-protein interactions...
December 21, 2018: Acta Tropica
Helen Ashwin, Karin Seifert, Sarah Forrester, Najmeeyah Brown, Sandy MacDonald, Sally James, Dimitris Lagos, Jon Timmis, Jeremy Mottram, Simon L Croft, Paul M Kaye
Background : Human visceral leishmaniasis, caused by infection with Leishmania donovani or L. infantum, is a potentially fatal disease affecting 50,000-90,000 people yearly in 75 disease endemic countries, with more than 20,000 deaths reported. Experimental models of infection play a major role in understanding parasite biology, host-pathogen interaction, disease pathogenesis, and parasite transmission. In addition, they have an essential role in the identification and pre-clinical evaluation of new drugs and vaccines...
2018: Wellcome Open Research
Neoklis Apostolopoulos, Athanasia Mitropoulou, Nina Thom, Andreas Moritz
Canine leishmaniasis is an emerging infection with increasing importance because the main vector also exists in Germany and autochthonous infections have been described. In this article we present the latest information available regarding therapy and prevention of this disease. Allopurinol-resistant Leishmania infantum strains were isolated from dogs which experienced recurrent disease while being treated with allopurinol, highlighting the need for alternative treatment options. Differing results of long-term studies on the efficacy of miltefosine in combination with allopurinol in comparison to meglumine antimoniate and allopurinol can affect the selection of the treatment protocol...
October 2018: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
Sandra González-de la Fuente, Esther Camacho, Ramón Peiró-Pastor, Alberto Rastrojo, Fernando Carrasco-Ramiro, Begoña Aguado, Jose M Requena
Leishmania braziliensis is the etiological agent of American mucosal leishmaniasis, one of the most severe clinical forms of leishmaniasis. Here, we report the assembly of the L. braziliensis (M2904) genome into 35 continuous chromosomes. Also, the annotation of 8395 genes is provided. The public availability of this information will contribute to a better knowledge of this pathogen and help in the search for vaccines and novel drug targets aimed to control the disease caused by this Leishmania species.
December 10, 2018: Memórias do Instituto Oswaldo Cruz
Pedro J Alcolea, Ana Alonso, Vicente Larraga
DNA vaccines require a vector to replicate genes and express encoding antigens. Antibiotic resistance genes are often used as selection markers, which must not be released to the environment upon final product commercialization. For this reason, generation of antibiotic resistance-free vectors is imperative. The pPAL vector contains the cytomegalovirus enhancer and promoter for expression in mammalian cells, and the E. coli fabI chromosomal gene as a selectable marker. The fabI gene encodes the enoyl-ACP reductase (FabI)...
December 6, 2018: Plasmid
Ines Lakhal-Naouar, Nancy Koles, Mangala Rao, Elaine B Morrison, John M Childs, Carl R Alving, Naomi E Aronson
Leishmaniasis is an expanding health threat worldwide complicated by the absence of an effective vaccine. We investigated transcutaneous immunization (TCI) as a needle-free immunization route which exploits the abundance of antigen presenting cells in the skin to induce both mucosal and systemic immunity. Leishmania (L.) major soluble antigens (SLA) or recombinant Leishmania homolog of receptors for activated C-kinase (rLACK) antigens were delivered transcutaneously together with cholera toxin (CT), to BALB/c mice...
December 5, 2018: 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
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