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Cloning, High-Level Gene Expression and Bioinformatics Analysis of Sp15 and Leif From Leishmania Major and Iranian Phlebotomus Papatasi Saliva As Single and Novel Fusion Proteins: A Potential Vaccine Candidate Against Leishmaniasis Publisher Pubmed



Bordbar A1, 3 ; Amanlou M2 ; Pooshang Bagheri K3 ; Ready PD4 ; Ebrahimi S1 ; Shahbaz Mohammadi H5 ; Ghafari SM1 ; Parvizi P1
Authors
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Authors Affiliations
  1. 1. Molecular Systematics Laboratory, Parasitology Department, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran, Iran
  2. 2. Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  3. 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
  5. 5. Department of Biochemistry, Genetics and Metabolism Research Group, Pasteur Institute of Iran, Tehran, Iran

Source: Transactions of the Royal Society of Tropical Medicine and Hygiene Published:2021


Abstract

Background: Early exacerbation of cutaneous leishmaniasis is mainly affected by both the salivary and Leishmania parasite components. Little is known of the vaccine combination made by immunogenic proteins of sandfly saliva (SP15) with Leishmania parasites (LeIF) as a single prophylactic vaccine, namely SaLeish. Also, there are no data available to determine the species-specific sequence of SP15 isolated from the Iranian Phlebotomus papatasi. Methods: Integrated bioinformatics and genetic engineering methods were employed to design, optimize and obtain a vector-parasite-based vaccine formulation in a whole-length fusion form of LeIF-SP15 against leishmaniasis. Holistic gene optimization was initially performed to obtain a high yield of pure 'whole-SaLeish' expression using bioinformatics analyses. Genomic and salivary gland RNAs of wild-caught P. papatasi were extracted and their complementary DNA was amplified and cloned into pJET vector. Results: The new chimeric protein of whole-SaLeish and randomly selected transcripts of native PpIRSP15 (GenBank accession nos. MT025054 and MN938854, MN938855 and MN938856) were successfully expressed, purified and validated by immunoblotting assay. Furthermore, despite the single amino acid polymorphisms of PpIRSP15 found at positions Y23 and E73 within the population of wild Iranian sandflies, antigenicity and conservancy of PpIRSP15 epitopes remained constant to activate T cells. Conclusions: The SaLeish vaccine strategy takes advantage of a plethora of vector-parasite immunogenic proteins with potential protective efficacy to stimulate both the innate and specific cellular immune responses against Leishmania parasites. © 2020 The Author(s). Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.
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