Hepatitis B virus core particles containing multiple epitopes confer protection against enterovirus 71 and coxsackievirus A16 infection in mice |
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| Affiliation: | 1. School of Life Sciences, Jilin University, Changchun, PR China;2. National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, PR China;3. Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, Changchun, PR China;4. Harbin Center for Disease Control and Prevention, Harbin 150056, PR China;5. State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, PR China;1. Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;2. National Center for Protein Science – Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China;1. BioMediTech, University of Tampere and Tampere University Hospital, Biokatu 6, FI-33014 University of Tampere, Finland;2. Vactech Ltd, Biokatu 8, FI-33520 Tampere, Finland;3. Department of Virology, School of Medicine, Biokatu 10, FI-33014 University of Tampere, Finland;4. School of Medicine, FI-33014 University of Tampere, Finland;5. Department of Biological and Environmental Science/Nanoscience Center, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Finland;6. Fimlab Laboratories, Pirkanmaa Hospital District, Biokatu 4, FI-33520 Tampere, Finland;7. The Center for Infectious Medicine, Department of Medicine HS, Karolinska Institutet, Karolinska University Hospital Huddinge F59, SE-141 86 Stockholm, Sweden;1. Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;2. National Center for Protein Science • Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China;1. Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China;2. Department of Microbiology and Immunology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China;3. Department of Dermatology, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China;4. Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA;1. The University of Queensland, Protein Expression Facility, Brisbane, QLD 4072, Australia;2. The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD 4072, Australia;3. Sentinext Therapeutics Sdn Bhd, Sains@USM, 10050 Penang, Malaysia |
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| Abstract: | ![]()
Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand-foot-and-mouth disease (HFMD). To investigate novel combined vaccines to prevent EV71 and CA16 infection, we constructed chimeric virus-like particles (tHBc/SPA or tHBc/SP VLPs) displaying conserved epitopes of EV71 (aa 208–222 of VP1 and aa 248–263 of VP2) and CA16 (aa271-285 of VP1) using a truncated hepatitis B virus core carrier (tHBc). Immunization with the chimeric VLPs induced epitope- or virus-specific IgG and neutralization antibodies against EV71 and CA16 in the mice. Compared with inactivated EV71, the chimeric VLPs induced significantly increased Th1 cytokine (IFN-γ, IL-2) production and decreased Th2 cytokine (IL-4, IL-10) responses. Neonatal mice born to dams immunized with the recombinant particles were completely protected from lethal EV71 and partially protected from CA16 infection. Co-expression of the conserved human MHC class I CD4+ T cell epitope (aa248-263 of VP2) did not improve the antiviral immunity of the chimeric VLP vaccine in mice. Our results demonstrate that experimental combination vaccines comprised of EV71 and CA16 epitopes induce both humoral and cellular immune responses and therefore support further preclinical and clinical development of a bivalent VLP vaccine targeting both CA16 and EV71. |
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| Keywords: | Virus like particles Immune protection Enterovirus 71 Coxsackievirus A16 |
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