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Human IgG Fc promotes expression,secretion and immunogenicity of enterovirus 71 VP1 protein
Authors:Juan Xu  Chunhua Zhang
Affiliation:1.Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 210029, China2.Department of Infectious Diseases3.China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China
Abstract:Enterovirus (EV71) can cause severe neurological diseases, but the underlying pathogenesis remains unclear. The capsid protein, viral protein 1 (VP1), plays a critical role in the pathogenicity of EV71. High level expression and secretion of VP1 protein are necessary for structure, function and immunogenicity in its natural conformation. In our previous studies, 5 codon-optimized VP1 DNA vaccines, including wt-VP1, tPA-VP1, VP1-d, VP1-hFc and VP1-mFc, were constructed and analyzed. They expressed VP1 protein, but the levels of secretion and immunogenicity of these VP1 constructs were significantly different (P<0.05). In this study, we further investigated the protein levels of these constructs and determined that all of these constructs expressed VP1 protein. The secretion level was increased by including a tPA leader sequence, which was further increased by fusing human IgG Fc (hFc) to VP1. VP1-hFc demonstrated the most potent immunogenicity in mice.Furthermore, hFc domain could be used to purify VP1-hFc protein for additional studies.
Keywords:enterovirus 71   VP1   DNA vaccine   human IgG Fc   immunogenicity
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