Intranasal immunization with chitosan microparticles enhances LACK-DNA vaccine protection and induces specific long-lasting immunity against visceral leishmaniasis |
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| Affiliation: | 1. Núcleo de Doenças Infecciosas, Universidade Federal Do Espírito Santo, Vitoria, Brazil;2. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Brazil;3. Division of Medicine, University College London, London, United Kingdom;4. Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;5. Instituto de Microbiologia Professor Paulo de Goes, Universidade Federal Do Rio de, Janeiro, Brazil;6. IMT Mines Albi-Carmaux, Campus Jarlard, Université de Toulouse, France;1. Departamento de Microbiología e Inmunología, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta Nacional 36, Km 601, X5804ZAB Río Cuarto, Córdoba, Argentina;2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina;1. Laboratorio de Inmunoquímica y Biotecnología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil, Buenos Aires, Argentina;2. Servicio Bacteriología, Departamento Laboratorio del Instituto Nacional de Epidemiología “Dr. Juan H. Jara” (INE), Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos G. Malbrán” (ANLIS), Ministerio de Salud de la Nación, Argentina;3. Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile;1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China;2. Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China;3. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China;1. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China;2. Department of Infectious Medicine, Beijing Children''s Hospital, Capital Medical University, National Center for Children''s Health, Beijing, China;1. Dept. Infection Biology, Institute of Infection and Global Health, University of Liverpool, L3 5RF, UK;2. Centre Eugène Marquis, Université Rennes-1, INSERM U1242, Rennes, France;3. Graduate Studies Office, Department of Research, Innovation and Graduate Studies, Waterford Institute of Technology, X91 K0EK, Ireland |
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| Abstract: | Development of a protective vaccine against Leishmania depends on antigen formulation and adjuvants that induce specific immunity and long-lasting immune responses. We previously demonstrated that BALB/c mice intranasally vaccinated with a plasmid DNA encoding the p36/LACK leishmanial antigen (LACK-DNA) develop a protective immunity for up to 3 months after vaccination, which was linked with the systemic expression of vaccine mRNA in peripheral organs. In this study, LACK-DNA vaccine was associated with biocompatible chitosan microparticles cross-linked with glyceraldehyde (CMC) to boost the long-lasting immunity against the late Leishmania infantum challenge. Infection at 7 days, 3 or 6 months after vaccination resulted in significantly lower parasite loads when compared with non-vaccinated controls. Besides, LACK-DNA-chitosan vaccinated mice showed long-time protection observed after the late time point challenge. The achieved protection was correlated with an enhanced spleen cell responsiveness to parasite antigens, marked by increased proliferation and IFN-γ as well as decreased IL-10 production. Moreover, we found diminished systemic levels of TNF-α that was compatible with the better health condition observed in LACK-DNA/CMC vaccinated-infected mice. Together, our data indicate the feasibility of chitosan microparticles as a delivery system tool to extend the protective immunity conferred by LACK-DNA vaccine, which may be explored in vaccine formulations against Leishmania parasite infections. |
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| Keywords: | Visceral leishmaniasis Intranasal delivery DNA vaccine LACK |
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