Alternative strategy for visceral leishmaniosis control: HisAK70-Salmonella Choleraesuis-pulsed dendritic cells |
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| Institution: | 1. INMIVET, Department of Animal Health, Faculty of Veterinary Science, Complutense University of Madrid, 28040 Madrid, Spain;2. Department of Animal Health, Faculty of Veterinary Science, Complutense University of Madrid, 28040 Madrid, Spain;1. School of Biomedical Sciences, University of Queensland, Australia;2. The Wesley-St Andrew’s Research Institute, Toowong, Australia;1. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA;2. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA;1. Pharmacy and Pharmaceutical Technology Department, University of Navarra, Pamplona, Spain;2. Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain;3. Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain;4. Chemical & Environmental Engineering Department & Nanoscience Institute of Aragon, University of Zaragoza, Zaragoza, Spain;5. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Madrid, Spain |
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| Abstract: | Here, we describe a novel approach that exploits an attenuated mutant of Salmonella enterica serovar Choleraesuis as carrier to deliver a plasmid encoding protein HisAK70. Subsequently, dendritic cells (DCs) were pulsed with this vaccine vector. The aim of this study was to evaluate the effectiveness of the prepared HisAK70-S. Choleraesuis-pulsed DCs (HisAK70-SAL DCs) against visceral leishmaniosis (VL). In our ex vivo model of infection, the prepared formulations could decrease parasite growth by up to 80% by augmenting the production of IL-12p40 and by reducing arginase activity (ARG). Also, BALB/c mice when immunised with this formulation showed significant reduction in parasite burden in both spleen (20% of reduction) and liver (75% of reduction). The balance of the immune ratios IFN-γ/IL-10, TNF-α/IL-10, and IgG2a/IgG1 reflected the acquisition of an improved resistant phenotype in HisAK70-SAL DCs vaccinated mice compared to control mice. Our results suggest that HisAK70-SAL DCs could be a promising alternative approach for vaccine delivery that has the potential to fight Leishmania infantum (L. infantum) infection. |
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| Keywords: | Vaccination HisAK70 Dendritic cells |
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