Modular\nDisplay of <i>Plasmodium yoelii</i> Circumsporozoite Surface\nProtein and Merozoite Surface Protein-1\non Norovirus-like Particles

Recently, virus-like particles have been regarded as\na promising\nplatform for displaying foreign peptides or proteins on their surface.\nIn this study, a dual-protein-displaying platform based on the norovirus-like\nparticle (NoV-LP) was developed using SpyTag (SpT)/SpyCatcher (SpC)\nprotein bioconjugation. A short 14-amino-acid SpT peptide was added\nto the C-terminus of VP1, with a rigid “EAAAK” spacer\nin between. Antigenic proteins from a rodent malaria parasite, <i>Plasmodium yoelii</i>, specifically the circumsporozoite protein\n(PyCSP) and the 19 kDa C-terminal region of merozoite surface protein\n1 (PyMSP1<sub>19</sub>), were displayed on the surface of NoV-LPs\nin both monovalent and bivalent formats. The immunogenicity of these\nVLP-based vaccines was assessed, and they were found to induce antigen-specific\nIgG responses against both PyCSP and PyMSP1<sub>19</sub> in BALB/c\nmice in the absence of an adjuvant, at levels comparable to those\ninduced by subunit antigenic proteins with an alum adjuvant added.\nInterestingly, the bivalent vaccine raised IgG responses at a similar\ntiter to the monovalent vaccine. This finding hints that the NoV-LP\npossesses an inherent adjuvanted property in the presence of a foreign\nantigen. The measured anti-PyCSP and anti-PyMSP1<sub>19</sub> antibodies\nthrough ELISA indicate that surface display of PyCSP and PyMSP1<sub>19</sub> on SpTagged-NoV-LP has the potential for further development\nas a bivalent vaccine against two different life-cycle stages of malaria.