Engineered virus-like particle nanoplatforms for next-generation vaccines: antigen display, immune potentiation, and physicochemical stabilization

Abstract Background Virus-like particles (VLPs) are genome-free, self-assembled nanostructures increasingly engineered from passive antigen mimics into multifunctional nanoplatforms integrating antigen display, innate immune activation, and physicochemical stability. Swine viral diseases, including foot-and-mouth disease (FMD), African swine fever (ASF), and porcine reproductive and respiratory syndrome (PRRS), provide a stringent translational testbed for these platforms within a broader reverse-translation and One Health framework. Conventional live attenuated and inactivated vaccines remain limited by reversion risk, immune interference, suboptimal cell-mediated immunity, cold-chain dependence, and incomplete compatibility with differentiating infected from vaccinated animals (DIVA) strategies. Main body Beyond serving as structural antigen mimics, VLPs can be engineered as modular nanoplatforms that shape innate immune sensing, B-cell receptor cross-linking, and MHC class I cross-presentation. Using swine viral diseases as a translational animal model, we examine VLP performance as a function not only of antigen selection, but also of expression system, scaffold geometry, surface engineering, encapsulated immunostimulants, and physicochemical stabilization. We focus on five interrelated themes: the immunological basis of VLP activity; production platforms for non-enveloped and enveloped VLPs; surface-display and plug-and-display strategies, including SpyTag/SpyCatcher coupling and self-assembling protein nanoparticles; adjuvant encapsulation and inorganic coating, including calcium-phosphate biomineralization and metal–organic-framework coatings; and translational constraints related to scale-up, regulation, species-specific immune translation, and field deployment. Conclusions Current evidence suggests that next-generation VLP vaccines may benefit from moving beyond simple structural mimicry toward multifunctional nanoplatforms that integrate antigen display, immune potentiation, and physicochemical stabilization within a single particle architecture. The central conceptual contribution of this review is a tiered framework in which these functions converge into triple-function nanoplatforms. The translational value of such systems will depend on rigorous validation in porcine models, reproducible manufacturing, thermostability under realistic handling, and evaluation under maternal-antibody interference and mucosal-delivery constraints.