title: A Modular Vaccine Development Platform Based on Sortase-Mediated Site-Specific Tagging of Antigens onto Virus-Like Particles.
abstract: Virus-like particles (VLPs) can be used as powerful nanoscale weapons to fight against virus infection. In addition to direct use as vaccines, VLPs have been extensively exploited as platforms on which to display foreign antigens for prophylactic vaccination and immunotherapeutic treatment. Unfortunately, fabrication of new chimeric VLP vaccines in a versatile, site-specific and highly efficient manner is beyond the capability of traditional VLP vaccine design approaches, genetic insertion and chemical conjugation. In this study, we described a greatly improved VLP display strategy by chemoenzymatic site-specific tailoring antigens on VLPs surface with high efficiency. Through the transpeptidation mediated by sortase A, one protein and two epitopes containing N-terminal oligoglycine were conjugated to the LPET motif on the surface of hepatitis B virus core protein (HBc) VLPs with high density. All of the new chimeric VLPs induced strong specific IgG responses. Furthermore, the chimeric VLPs with sortase A tagged enterovirus 71 (EV71) SP70 epitope could elicit effective antibodies against EV71 lethal challenging as well as the genetic insertion chimeric VLPs. The sortase A mediated chemoenzymatic site-specific tailoring of the HBc VLP approach shows great potential in new VLP vaccine design for its simplicity, site specificity, high efficiency, and versatility.
authors.affiliation: Unit of Herpesvirus and Molecular Virology, Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shubing
authors.initials: S
authors.lastname: Tang
authors.affiliation: Unit of Herpesvirus and Molecular Virology, Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Baoqin
authors.initials: B
authors.lastname: Xuan
authors.affiliation: Unit of Vaccinology and Antiviral Strategies, Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Ye
authors.affiliation: Unit of Vaccinology and Antiviral Strategies, Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Unit of Herpesvirus and Molecular Virology, Key Laboratory of Molecular Virology &Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Qian
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006509:Hepatitis B / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D008807:Mice, Inbred BALB C; D014758:Viral Core Proteins / Q000378:metabolism*; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D014758:Viral Core Proteins; D014765:Viral Vaccines; D003546:Cysteine Endopeptidases