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The enhanced immune response of hepatitis B virus DNA vaccine using SiO2@LDH nanoparticles as an adjuvant
Institution:1. Tenth People''s Hospital, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR China;2. Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China;1. State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai 200433, China;2. Group for Advanced Nanocomposite Engineering, Department of Chemical Engineering, Curtin University, Perth 6102, Australia;1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Australia;2. School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia;3. Department of Chemical Engineering, Curtin University, Australia;1. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China;2. School of Science, Engineering and Technology, Abertay University, Kydd Building, Dundee DD1 1HG, Scotland, UK;1. Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, PR China;2. Tongji Hospital, Tongji University, PR China
Abstract:Various approaches have been used to improve systemic immune response to infectious disease or virus, and DNA vaccination has been demonstrated to be one of these effective ways to elicit protective immunity against pathogens. Our previous studies showed that layered double hydroxides (LDH) nanoparticles could be efficiently taken up by the MDDCs and had an adjuvant activity for DC maturation. To further enhance the immune adjuvant activity of LDH, core–shell structure SiO2@LDH nanoparticles were synthesized with an average diameter of about 210 nm. And its high transfection efficiency in vitro was demonstrated by using GFP expression plasmid as model DNA. Exposing SiO2@LDH nanoparticles to macrophages caused a higher dose-dependent expression of IFN-γ, IL-6, CD86 and MHC II, compared with SiO2 and LDH respectively. Furthermore, in vivo immunization of BALB/c mice indicated that, DNA vaccine loaded-SiO2@LDH nanoparticles not only induced much higher serum antibody response than naked DNA vaccine and plain nanoparticles, but also obviously promoted T-cell proliferation and skewed T helper to Th1 polarization. Additionally, it was proved that the caveolae-mediated uptake of SiO2@LDH nanoparticles by macrophage lead to macrophages activation via NF-κB signaling pathway. Our results indicate that SiO2@LDH nanoparticles could serve as a potential non-viral gene delivery system.
Keywords:Layered double hydroxides  DNA vaccine  Hepatitis B surface antigen  Adjuvant  Immunology  Macrophages
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