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Leishmania Vaccine

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...
July 17, 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
Fan Yang, Xuemei Fan, He Huang, Qiujie Dang, Hongwei Lei, Yang Li
A single epitope of Leishmania analog of the receptors for activated C kinase (LACK) from Leishmania major , the polypeptide LACK156-173 , is recognized by Vβ4+ /Vα8+ T cells, and activate these cells that drives the subsequent T helper (Th)2 response. This study was undertaken to investigate the therapeutic potential of the LACK156-173 epitope in murine autoimmune arthritis models. To explore the influence of the LACK156-173 epitope on murine collagen antibody-induced arthritis, as well as its immunological mechanism, we vaccinated or treated mice with a LACK156-173 epitope expression plasmid or polypeptide...
2018: Frontiers in Immunology
Manish K Singh, Fauzia Jamal, Amit K Dubey, Pushkar Shivam, Sarita Kumari, Pushpanjali, Chayanika Bordoloi, S Narayan, V N R Das, K Pandey, P Das, Shubhankar K Singh
The shift of macrophage and T-cell repertoires towards proinflammatory cytokine signalling ensures the generation of host-protective machinery that is otherwise compromised in cases of the intracellular Leishmania parasite. Different groups have attempted to restore host protective immunity. These vaccine candidates showed good responses and protective effects in murine models, but they generally failed during human trials. In the present study, we evaluated the effect of 97 kDa recombinant nucleoporin-93 of Leishmania donovani (rLd-NUP93) on mononuclear cells in healthy and treated visceral leishmaniasis (VL) patients and on THP-1 cell lines...
July 9, 2018: Cytokine
Harpreet Kaur, Ankita Thakur, Sukhbir Kaur
Background: Currently, there is no vaccine available for any form of leishmaniasis for human use, including visceral leishmaniasis (VL). The treatment relies on drugs associated with severe toxic side effects and increased parasite drug resistance. At present, there is a strong need to develop and implement a successful vaccine against this disease. Therefore, we evaluated immunoprophylactic potential of a cocktail of low molecular weight antigens along with various adjuvants. Methods: The three antigens (2015, Department of Zoology, Panjab University, Chandigarh), 31kDa, 36 kDa and 51 kDa of L...
January 2018: Iranian Journal of Parasitology
Shamsi Noorpisheh Ghadimi, Shirin Farjadian, Gholam Reza Hatam, Mehdi Kalani, Bahador Sarkari
BACKGROUND: Toll like receptors play a major role in immune responses against Leishmania parasites. OBJECTIVE: To evaluate the efficacy of vaccination with live attenuated L. major and TLR4 agonist in protection against L. major infection. METHODS: Attenuated L. major was prepared by continuous sub-culturing of the parasite. A total of 90 mice were assigned to 9 groups including 6 groups of BALB/c (G1-6) and 3 groups (G7-9) of C57BL/6 mice...
June 2018: Iranian Journal of Immunology: IJI
Rintaro Iwata Hara, Aya Yaoita, Katsuya Takeda, Hiroaki Ueki, Ayumu Ishii, Hideyuki Imoto, Satoshi Kobayashi, Michi Sano, Mihoko Noro, Kazuki Sato, Takeshi Wada
Bacterial and protozoan sugar chains contain glycosyl 1-phosphate repeating structures; these repeating structures have been studied for vaccine development. The fluorinated analogues of [β-Gal-(1→4)-α-Man-(1→6)-P-] n , which are glycosyl 1-phosphate repeating structures found in Leishmania , were synthesised using the solid-phase phosphoramidite method. This method has been less extensively studied for the synthesis of glycosyl 1-phosphate units than H -phosphonate chemistry. A stepwise synthesis of a compound containing five such repeating units has been conducted using the phosphoramidite method herein, which is the longest glycosyl 1-phosphate structures to be chemically constructed in a stepwise manner...
June 2018: ChemistryOpen
Negar Seyed, Nathan C Peters, Sima Rafati
Leishmaniasis is a health-threatening vector-borne disease in almost 90 different countries. While a prophylactic human vaccine is not yet available, the fact that recovery from leishmaniasis establishes lifelong immunity against secondary infection suggests that a vaccine is attainable. In the past, deliberate infection with virulent parasites, termed Leishmanization, was used as a live-vaccine against cutaneous leishmaniasis and effectively protected against vector-transmitted disease in endemic areas. However, the practice was discontinued due to major complications including non-healing skin lesions, exacerbation of skin diseases, and the potential impact of immunosuppression...
2018: Frontiers in Immunology
Rakesh K Singh, Sreenivas Gannavaram, Nevien Ismail, Amit Kaul, Mallikarjuna Rao Gedda, Hira L Nakhasi
The protozoan parasite Leishmania has evolved several strategies to undermine host defense mechanisms by inducing Th2-type adaptive immunity and suppressing effector functions of Th1 phenotype. In our earlier studies, using centrin gene-deleted Leishmania (LdCen-/- ) parasites as an immunogen, we have shown induction of an effective Th1-type immunity and robust memory responses that mediate protection against virulent challenge. However, role of inhibitory signals in Leishmania vaccine induced immunity in general, and LdCen-/- in particular has not been studied...
2018: Frontiers in Immunology
Daniel S Dias, Patrícia A F Ribeiro, Vívian T Martins, Daniela P Lage, Lourena E Costa, Miguel A Chávez-Fumagalli, Fernanda F Ramos, Thaís T O Santos, Fernanda Ludolf, Jamil S Oliveira, Tiago A O Mendes, Eduardo S Silva, Alexsandro S Galdino, Mariana C Duarte, Bruno M Roatt, Daniel Menezes-Souza, Antonio L Teixeira, Eduardo A F Coelho
Vaccination seems to be the best approach to control visceral leishmaniasis (VL). Resistance against infection is based on the development of a Th1 immune response characterized by the production of interferons-γ (IFN-γ), interleukin-12 (IL-12), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α), among others. A number of antigens have been tested as potential targets against the disease; few of them are able to stimulate human immune cells. In the present study, 1 prediction of MHC class I and II molecules-specific epitopes in the amino acid sequences of 3 Leishmania proteins: 1 hypothetical, prohibitin, and small glutamine-rich tetratricopeptide repeat-containing proteins, was performed using bioinformatics tools, and a T-cell epitopes-based recombinant chimeric protein was constructed, synthetized and purified to be evaluated in invitro and in vivo experiments...
May 22, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Helen A Fletcher, Mitali Chatterjee, Andrea Cooper, Tracy Hussell, Paul M Kaye, Joann Prior, Rajko Reljic, Samantha Vermaak, Martin Vordermeier, Ann Williams, Helen McShane
For several complex intracellular pathogens, we have an urgent need for effective vaccines and yet there are common barriers to vaccine development. These diseases, including tuberculosis, leishmaniasis, leprosy and melioidosis, cause a huge burden of disease and disproportionately affect low and middle income countries. They are therefore often neglected due to the marginalisation of affected populations and the poor predicted commercial return on investment. Barriers to vaccine development include an incomplete understanding of protective immunity and translation from the bench into clinical vaccine trials...
2018: F1000Research
Farnaz Zahedifard, Sima Rafati
Leishmaniasis is one of the neglected tropical diseases and is highly endemic in many countries. Currently, there is no adequate human vaccine and treatment to control the disease. Areas covered: As a result of the failure of chemotherapy and toxicity, it is necessary to find another approach for the treatment of leishmaniasis. Recently, antimicrobial peptides (AMPs), originating from natural resources, have attracted much attention for their use as a new antibiotics for many infectious and noninfectious diseases...
June 2018: Expert Review of Anti-infective Therapy
Mehdi Azami, Vahid Ranjkesh Adermanabadi, Hossein Khanahmad, Mohammad Ali Mohaghegh, Ebtesam Zaherinejad, Maryam Aghaei, Akram Jalali, Seyed Hossein Hejazi
Leishmania infantum is the causative agent of infantile visceral leishmaniasis (VL) in the Mediterranean region. Despite developing protective responses, the disease progresses due to many of factors. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue, and defective humoral response. Genetic changes that occur inside the genome of alienated or parasite cells, along with immune responses, play an important role in controlling or progressing the disease...
2018: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
Neelam Prakash Bodhale, Subhashis Pal, Sunil Kumar, Debprasad Chattopadhyay, Bhaskar Saha, Naibedya Chattopadhyay, Maitree Bhattacharyya
Leishmania donovani is a protozoan parasite that infects mammalian macrophages, wherein the parasite resides and replicates as amastigotes, inflicting the potentially fatal disease visceral leishmaniasis. The disease is characterized by severe immunosuppression and hypocholesterolemia implying metabolic changes in L. donovani infection; whether such metabolic changes are also linked to susceptibility to the infection is not known. Herein, four inbred mouse strains were first characterized for their resistance or susceptibility profile to L...
June 6, 2018: Cytokine
Patrícia A F Ribeiro, Daniel S Dias, Daniela P Lage, Lourena E Costa, Vívian T Martins, Grasiele S V Tavares, Débora V C Mendonça, Mariana P Lima, Jamil S Oliveira, Bethina T Steiner, Ricardo A Machado-de-Ávila, Bruno M Roatt, Miguel A Chávez-Fumagalli, Daniel Menezes-Souza, Mariana C Duarte, Antonio L Teixeira, Eduardo A F Coelho
Visceral leishmaniasis (VL) is a fatal disease when acute and untreated. The treatment against this disease is long and presents toxicity and/or high costs. Moreover, parasite resistance has been increasing. Therefore, alternative control measures to avoid the spread of disease should be considered. It is accepted that the development of the T helper (Th)1 immune response, based on the production of pro-inflammatory cytokines, is required for the control of parasites. Although recombinant protein-based vaccines have been tested against VL, they require supplementation with immune adjuvants...
May 29, 2018: Cellular Immunology
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