Modular Vaccine Platform Based on the Norovirus-Like Particle

Abstract

Virus-like particle (VLP) vaccines have recently emerged as a safe and effective alternative to conventional vaccine technologies. In addition to using VLPs as vaccines against the viruses they derive from, their strong immunogenic effects can be harnessed for making vaccines against other pathogens by decorating VLP surface with antigens from the pathogen. We covalently decorated the robust norovirus-like particle with two conserved influenza antigens using SpyCatcher/SpyTag conjugation technology (PMID: 22366317), and tested for the immunogenicity of the resulting vaccine candidates in BALB/c mice.<br/>SpyTagged noro-VLP was expressed with high efficiency in insect cells and purified using industrially scalable methods. Like the native noro-VLP, SpyTagged noro-VLP is stable for months when refrigerated in a physiological buffer. We studied the morphology and size of the tagged and decorated noro-VLP with transmission electron microscopy and compared the results to dynamic light scattering. The conserved influenza antigens were produced separately as SpyCatcher fusions in E. coli before covalent conjugation on the surface of noro-VLP. Producing the antigenic pathogen fragments and the VLP platform separately makes vaccine development rapid and convenient. The noro-VLP had a high adjuvant effect, inducing high titers of antibody production against proteins presented on its surface. The modular noro-VLP vaccine platform presented here offers a rapid, convenient and safe method to present various soluble protein antigens to the immune system for vaccination and antibody production purposes.<br/>