title: Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.
abstract: Dengue viruses (DENVs) are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV) composed of UV-inactivated DENV-2 (UVI-DENV) and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs) loaded into chitosan nanoparticles (CS-NPs). CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs) resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR) and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Taweewun
authors.initials: T
authors.lastname: Hunsawong
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Panya
authors.initials: P
authors.lastname: Sunintaboon
authors.affiliation: Tuberculosis Research Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
authors.forename: Saradee
authors.initials: S
authors.lastname: Warit
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Butsaya
authors.initials: B
authors.lastname: Thaisomboonsuk
authors.affiliation: Viral Disease Branch, Walter Reed Army Institute of Research, Bethesda, Maryland, United States of America.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jarman
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Yoon
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Sukathida
authors.initials: S
authors.lastname: Ubol
authors.affiliation: The United States Army Medical Materiel Development Activity, Fort Detrick, Maryland, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fernandez
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000942:Antigens, Bacterial / Q000378:metabolism*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D048271:Chitosan / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D053059:Dengue Vaccines / Q000276:immunology* / Q000378:metabolism; D003716:Dengue Virus / Q000276:immunology*; D004705:Endocytosis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000378:metabolism; D009163:Mycobacterium bovis / Q000737:chemistry*; D053758:Nanoparticles / Q000378:metabolism* / Q000648:ultrastructure; D015164:Vaccines, Inactivated / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D053059:Dengue Vaccines; D006684:HLA-DR Antigens; D015164:Vaccines, Inactivated; D048271:Chitosan