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Leishmania Vaccine

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...
October 12, 2018: 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...
October 11, 2018: Trends in Parasitology
Jinlei He, Fan Huang, Jianhui Zhang, Han Chen, Qiwei Chen, Junrong Zhang, Jiao Li, Zhiwan Zheng, Jianping Chen, Dali 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, -A24 and -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, -A24 and -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...
September 12, 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
Gerusa B Carvalho, Lourena E Costa, Daniela P Lage, Fernanda F Ramos, Thaís T O Santos, Patrícia A F Ribeiro, Daniel S Dias, Beatriz C S Salles, Mariana P Lima, Lívia M Carvalho, Ana C S Dias, Patrícia T Alves, Michelle L Franklin, Renata A M Silva, Mariana C Duarte, Daniel Menezes-Souza, Bruno M Roatt, Miguel A Chávez-Fumagalli, Luiz Ricardo Goulart, Antonio L Teixeira, Eduardo A F Coelho
In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments...
September 10, 2018: Parasitology
Maria Agallou, Eleni Pantazi, Elisavet Tsiftsaki, Dimitra K Toubanaki, Catherine Gaitanaki, Despina Smirlis, Evdokia Karagouni
Leishmania elongation factor 2 (EF-2) has been previously identified as a TH 1-stimulatory protein. In this study, we assayed the protective potential of the N-terminal domain of EF-2 (N-LiEF-2, 1-357 aa) that has been predicted to contain several overlapping MHC class I and II-restricted epitopes injected in the form of dendritic cell (DC)-based vaccine. Ex vivo pulsing of DCs with the recombinant N-LiEF-2 domain along with CpG oligodeoxynucleotides (ODNs) resulted in their functional differentiation. BALB/c vaccinated with CpG-triggered DCs pulsed with N-LiEF-2 were found to be the most immune-reactive in terms of induction of DTH responses, increased T cell proliferation and IL-2 production...
August 30, 2018: Molecular Immunology
Bahareh Vakili, Mahboobeh Eslami, Gholam Reza Hatam, Bijan Zare, Nasrollah Erfani, Navid Nezafat, Younes Ghasemi
Visceral leishmaniasis (VL) or kala-azar, the most severe form of the disease, is endemic in more than eighty countries across the world. To date, there is no approved vaccine against VL in the market. Recent advances in reverse vaccinology could be promising approach in designing the efficient vaccine for VL treatment. In this study, an efficient multi-epitope vaccine against Leishmania infantum, the causative agent of VL, was designed using various computational vaccinology methods. Potential immunodominant epitopes were selected from four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP)...
December 2018: International Journal of Biological Macromolecules
Patrícia A F Ribeiro, Daniel S Dias, Marcus V M Novais, Daniela P Lage, Grasiele S V Tavares, Débora V C Mendonça, Jamil S Oliveira, Miguel A Chávez-Fumagalli, Bruno M Roatt, Mariana C Duarte, Daniel Menezes-Souza, Fernanda Ludolf, Carlos A P Tavares, Mônica C Oliveira, Eduardo A F Coelho
Leishmania proteins have been evaluated as vaccine candidates against leishmaniasis; however, most antigens present low immunogenicity and need to be added with immune adjuvants. A low number of licensed adjuvants exist on the market today; therefore, research conducted to produce new products is desirable. The present study sought to evaluate the immunogenicity and protective efficacy of a recombinant Leishmania hypothetical protein, namely LiHyR, administered with saponin or liposomes in BALB/c mice. Immunological and parasitological parameters were evaluated, and results showed significant protection against Leishmania infantum infection produced by both compositions in the immunized animals; however, this was not identified when the antigen was used alone...
August 21, 2018: Cytokine
Jair L Siqueira-Neto, Anjan Debnath, Laura-Isobel McCall, Jean A Bernatchez, Momar Ndao, Sharon L Reed, Philip J Rosenthal
Cysteine proteases (CPs) play key roles in the pathogenesis of protozoan parasites, including cell/tissue penetration, hydrolysis of host or parasite proteins, autophagy, and evasion or modulation of the host immune response, making them attractive chemotherapeutic and vaccine targets. This review highlights current knowledge on clan CA cysteine proteases, the best-characterized group of cysteine proteases, from 7 protozoan organisms causing human diseases with significant impact: Entamoeba histolytica, Leishmania species (sp...
August 2018: PLoS Neglected Tropical Diseases
Fatemeh Khadir, Christopher R Shaler, Ahmad Oryan, Patrick T Rudak, Delfina M Mazzuca, Tahereh Taheri, Jimmy D Dikeakos, S M Mansour Haeryfar, Sima Rafati
Leishmaniasis is a serious global health problem affecting many people worldwide. While patients with leishmaniasis can be treated with several agents, drug toxicicty and the emergence of resistant strains render available treatments ineffective in the long run. Inhibitors of the mammalian target of rapamycin (mTOR) have been demonstrated to exert anti-pathogen properties. In this study, we tested the therapeutic efficacy of several mTOR inhibitors in controlling infection with Leishmania major. Rapamycin, GSK-2126458 and KU-0063794 were administered to BALB/c mice, which had received an intrafootpad injection of the parasite...
August 2018: PLoS Neglected Tropical Diseases
Matteo Rossi, Nicolas Fasel
In nature, humans infected with protozoan parasites can encounter viruses, which could alter their host immune response. The impact of viruses on human parasitic diseases remains largely unexplored due to the highly sterilized environment in experimental studies and the difficulty to draw a correlation between co-infection and pathology. Recent studies show that viral infections exacerbate pathology and promote dissemination of some Leishmania infections, based on a hyper-inflammatory reaction driven by type I interferons...
August 7, 2018: Current Opinion in Microbiology
Oghlniaz Jorjani, Fatemeh Ghaffarifar, Zohreh Sharifi, Abdolhossein Dalimi, Hajar Ziaei-Hezarjaribi, Benyamin Talebi
Background: Leishmaniasis is caused by parasitic protozoa of the genus Leishmania which is an obligate intracellular parasite in the infected host. Individuals who have been recovered from clinical leishmaniasis develop strong immunity against reinfection. DNA vaccines are the new type of vaccines that induce expression of protein eukaryotic cells. DNA vaccines can be stimulated by the cellular and humoral immune responses using one or several genes. Methods: A DNA vaccine containing plasmids encoding the pcLACK+pcTSA genes of Leishmania major (L...
July 2018: Avicenna Journal of Medical Biotechnology
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
In Brazil, canine visceral leishmaniasis (CVL) is caused by Leishmania infantum , presenting a broad spectrum of clinical manifestations. Dogs are the main parasite reservoir in urban areas and canine cases precede human infection. Currently, A2 protein-based Leish-Tec® vaccine is the only vaccine commercially available against CVL in Brazil. Considering that the main screening and confirmatory tests of canine infection are serological, it is possible that the antibody response elicited after vaccination interfere with diagnosis, leading to the inability to distinguish between vaccinated and infected animals...
2018: Frontiers in Immunology
Ana Maria Murta Santi, Juliane Sousa Lanza, Luiza Guimarães Tunes, Jacqueline Araújo Fiuza, Gaétan Roy, Alessandra da Silva Orfanó, Andréa Teixeira de Carvalho, Frédéric Frézard, André Luís Branco de Barros, Silvane Maria Fonseca Murta, Rubens Lima do Monte-Neto
There is no safe and efficacious vaccine against human leishmaniasis available and live attenuated vaccines have been used as a prophylactic alternative against the disease. In order to obtain an attenuated Leishmania parasite for vaccine purposes, we generated L. infantum KHARON1 (KH1) null mutants (ΔLikh1). This gene was previously associated with growth defects in L. mexicana. ΔLikh1 was obtained and confirmed by PCR, qPCR and Southern blot. We also generate a KH1 complemented line with the introduction of episomal copies of KH1...
August 2, 2018: Scientific Reports
Samira Elikaee, Mehdi Mohebali, Sassan Rezaei, Hamid Eslami, Ali Khamesipour, Hossein Keshavarz, Mohammad Reza Eshraghian
Genetically modifying Leishmania major by eliminating essential virulence genes have been proposed as potential vaccine candidates. p27 is a COX component that is responsible for ATP synthesis. In this study a new mutant of Leishmania major (L. major) (MRHO/IR/75/ER) lacking the p27 gene (Lmp27- / - ) was produced via homologous recombination, marking the first time such a strain has been developed. In vitro macrophage infectivity and In vivo safety, and overall immunogenicity were evaluated at various time periods following inoculation into BALB/c mice...
October 2018: Cellular Immunology
Nazia Khatoon, Rajan Kumar Pandey, Rupal Ojha, Veeranarayanan Surya Aathmanathan, Muthukalingan Krishnan, Vijay Kumar Prajapati
Visceral Leishmaniasis (VL) is a deadly parasitic infection which affects poorest to poor population living in the endemic countries. Increasing resistant to existing drugs, disease burden and a significant number of deaths, necessitates the need for an effective vaccine to prevent the VL infection. This study employed a combinatorial approach to develop a multi-epitope subunit vaccine by exploiting Leishmania donovani membrane proteins. Cytotoxic T- and helper T-lymphocyte binding epitopes along with suitable adjuvant and linkers were joined together in a sequential manner to design the subunit vaccine...
July 26, 2018: Journal of Biomolecular Structure & Dynamics
Eduardo Ontoria, Yasmina E Hernández-Santana, Ana C González-García, Manuel C López, Basilio Valladares, Emma Carmelo
Leishmania spp. is a protozoan parasite that affects millions of people around the world. At present, there is no effective vaccine to prevent leishmaniases in humans. A major limitation in vaccine development is the lack of precise understanding of the particular immunological mechanisms that allow parasite survival in the host. The parasite-host cell interaction induces dramatic changes in transcriptome patterns in both organisms, therefore, a detailed analysis of gene expression in infected tissues will contribute to the evaluation of drug and vaccine candidates, the identification of potential biomarkers, and the understanding of the immunological pathways that lead to protection or progression of disease...
2018: Frontiers in Cellular and Infection Microbiology
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