Leishmania tarentolae secreting the sand fly salivary antigen PpSP15 confers protection against Leishmania major infection in a susceptible BALB/c mice model |
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Affiliation: | 1. Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran;2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;3. Research Center in Infectious Diseases, CHU de Québec Research Center and Department of Microbiology, Infectious Disease and Immunology, Laval University, Quebec (QC), Canada University, Quebec (QC), Canada;4. Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA;1. Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;2. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;3. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;4. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA;5. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA;6. UCLA AIDS Institute, Los Angeles, CA, USA;7. The Molecular Biology Institute, University of California, Los Angeles, CA, USA;1. School of Biological Sciences, University of Missouri—Kansas City, Kansas City, MO 64110, United States;2. Department of Biochemistry & Molecular Biophysics, Kansas State University, Manhattan, KS 66506, United States;1. Institute of Medical Microbiology, University of Duisburg-Essen, 45147 Essen, Germany;2. Department of Chemistry, University of Natural Resources and Life Sciences, 1190 Vienna, Austria;1. The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China;2. Biothera Solutions, formerly as Sinoasis Pharma, Ltd., Guangzhou, China;3. Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093, China;1. Cellular and Molecular Immunology Laboratory, Department of Laboratory Medicine, School of Tropical Medicine, 108, C. R. Avenue, Kolkata, 700073 West Bengal, India;2. Department of Human Physiology, University of Calcutta, 92, APC Road, Kolkata 700009, India;3. Laboratory of Virology, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India |
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Abstract: | Cutaneous leishmaniasis is a zoonotic, vector-borne disease causing a major health problem in several countries. No vaccine is available and there are limitations associated with the current therapeutic regimens. Immune responses to sand fly saliva have been shown to protect against Leishmania infection. A cellular immune response to PpSP15, a protein from the sand fly Phlebotomus papatasi, was sufficient to control Leishmania major infection in mice. This work presents data supporting the vaccine potency of recombinant live non-pathogenic Leishmania (L.) tarentolae secreting PpSP15 in mice and its potential as a new vaccine strategy against L. major. We generated a recombinant L. tarentolae-PpSP15 strain delivered in the presence of CpG ODN and evaluated its immunogenicity and protective immunity against L. major infection in BALB/c mice. In parallel, different vaccination modalities using PpSP15 as the target antigen were compared. Humoral and cellular immune responses were evaluated before and at three and eight weeks after challenge. Footpad swelling and parasite load were assessed at eight and eleven weeks post-challenge. Our results show that vaccination with L. tarentolae-PpSP15 in combination with CpG as a prime-boost modality confers strong protection against L. major infection that was superior to other vaccination modalities used in this study. This approach represents a novel and promising vaccination strategy against Old World cutaneous leishmaniasis. |
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Keywords: | Sand fly Saliva BALB/c mice CpG Vaccine |
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