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      Leishmania tarentolae: a vaccine platform to target dendritic cells and a surrogate pathogen for next generation vaccine research in leishmaniases and viral infections

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          Abstract

          Parasites of the genus Leishmania are unusual unicellular microorganisms in that they are characterized by the capability to subvert in their favor the immune response of mammalian phagocytes, including dendritic cells. Thus, in overt leishmaniasis, dendritic cells and macrophages are converted into a niche for Leishmania spp. in which the parasite, rather than being inactivated and disassembled, survives and replicates. In addition, Leishmania parasites hitchhike onto phagocytic cells, exploiting them as a mode of transport to lymphoid tissues where other phagocytic cells are potentially amenable to parasite colonization. This propensity of Leishmania spp. to target dendritic cells has led some researchers to consider the possibility that the non-pathogenic, reptile-associated Leishmania tarentolae could be exploited as a vaccine platform and vehicle for the production of antigens from different viruses and for the delivery of the antigens to dendritic cells and lymph nodes. In addition, as L. tarentolae can also be regarded as a surrogate of pathogenic Leishmania parasites, this parasite of reptiles could possibly be developed into a vaccine against human and canine leishmaniases, exploiting its immunological cross-reactivity with other Leishmania species, or, after its engineering, for the expression of antigens from pathogenic species. In this article we review published studies on the use of L. tarentolae as a vaccine platform and vehicle, mainly in the areas of leishmaniases and viral infections. In addition, a short summary of available knowledge on the biology of L. tarentolae is presented, together with information on the use of this microorganism as a micro-factory to produce antigens suitable for the serodiagnosis of viral and parasitic infections.

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          Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

          Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260
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            Leishmaniasis

            Leishmaniasis is a poverty-related disease with two main clinical forms: visceral leishmaniasis and cutaneous leishmaniasis. An estimated 0·7-1 million new cases of leishmaniasis per year are reported from nearly 100 endemic countries. The number of reported visceral leishmaniasis cases has decreased substantially in the past decade as a result of better access to diagnosis and treatment and more intense vector control within an elimination initiative in Asia, although natural cycles in transmission intensity might play a role. In east Africa however, the case numbers of this fatal disease continue to be sustained. Increased conflict in endemic areas of cutaneous leishmaniasis and forced displacement has resulted in a surge in these endemic areas as well as clinics across the world. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Major evidence gaps remain, and new tools are needed before leishmaniasis can be definitively controlled.
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              A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies

              Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites.
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                Author and article information

                Contributors
                claudio.bandi@unimi.it
                jairo.mendozaroldan@uniba.it
                domenico.otranto@uniba.it
                alessandro.alvaro@unimi.it
                louzadaviviane@gmail.com
                massimo.pajoro@gmail.com
                ilaria.varotto@unimi.it
                matteo.brilli@unimi.it
                alessandro.manenti@vismederi.com
                emanuele.montomoli@vismederi.com
                gianvincenzo.zuccotti@unimi.it
                sara.epis@unimi.it
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                26 January 2023
                26 January 2023
                2023
                : 16
                : 35
                Affiliations
                [1 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Biosciences, , Pediatric CRC “Romeo ed Enrica Invernizzi”–University of Milan, ; Milan, Italy
                [2 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Department of Veterinary Medicine, , University of Bari, ; Valenzano, Italy
                [3 ]GRID grid.511037.1, VisMederi, ; Siena, Italy
                [4 ]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Department of Molecular and Developmental Medicine, , University of Siena, ; Siena, Italy
                [5 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Biomedical and Clinical Sciences, , Pediatric CRC “Romeo ed Enrica Invernizzi”–University of Milan, ; Milan, Italy
                [6 ]Department of Pediatrics, Ospedale dei Bambini-Buzzi, Milan, Italy
                Article
                5651
                10.1186/s13071-023-05651-1
                9879565
                36703216
                79b3f0c2-6c9b-443f-ad13-6f608e0dc367
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 28 November 2022
                : 3 January 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100012032, Fondazione Romeo ed Enrica Invernizzi;
                Award ID: LIB_VT22CBAND
                Award ID: LIB_VT21SEPIS
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2023

                Parasitology
                protozoa,leishmaniasis,antigens,parasites,viral vaccines,immunization
                Parasitology
                protozoa, leishmaniasis, antigens, parasites, viral vaccines, immunization

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