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.
Highlights
Virus-like particles (VLPs) can be used as powerful nanoscale weapons to fight against virus infection
We attempted to ligate the AD-4 domain on glycoprotein B of human cytomegalovirus (HCMV) and two defined linear eptitopes of enterovirus 71 (EV71) to N-LPETGG-C VLPs under transpeptidation by sortase A
Design of sortase-mediated coupling system for site-specific linking of antigens to hepatitis B virus core protein (HBc) VLPs
Summary
Mediated Site-Specific Tagging of Antigens onto Virus-Like Particles received:07September2015 accepted: 21 April 2016. 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. 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. The existing approaches are not satisfactory to display different antigens on VLPs. In this study, we developed a simple and site-specific vaccine design approach with high efficiency. Antigens are covalently linked to HBc VLPs by chemoenzymatic site-specific coupling mediated by sortase A, sortagging for short, in one reaction. The novel vaccine design strategy proposed in our study surpasses traditional approaches and can be used to tailor VLP surfaces for further applications
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