A plant virus–based virus like-particle platform for therapeutic vaccination targeting IL-23A

Abstract Interleukin-23 (IL-23) is a pivotal cytokine in the pathogenesis of immune-mediated inflammatory diseases, making it an attractive therapeutic target. Vaccination against self-antigens offers an alternative to monoclonal antibody (mAb) therapies by eliciting endogenous Ab responses. Here, we report the development of a virus-like particle (VLP)–based vaccine targeting murine IL-23A (mIL23A) using the eggplant mosaic virus (EMV) coat protein as a carrier. mIL23A was incorporated either as a direct fusion or within a mosaic system, with the latter supporting efficient VLP assembly. Alternative antigen presentation strategies employed synthetic coiled-coil and zipper pairs. All constructs were expressed in E. coli , purified, and characterized by SDS-PAGE, TEM, and DLS. Immunization of BALB/c mice elicited robust mIL23A-specific Abs, with mosaic VLPs inducing high-avidity, Th1-biased responses. Encapsidated RNA within VLPs was double-stranded and stimulated TLR3, enhancing immunogenicity. Scale-up in bioreactors preserved VLP integrity and antigen incorporation, yielding 1.72 mg per gram of cells. These results establish EMV VLPs as a flexible and scalable platform for presenting challenging antigens and provide a promising approach for therapeutic vaccination against self-antigens.