Nanovaccines: Antigen selection, stabilization, adjuvantation, formulation, and evaluation

Engineered nanovaccines offer transformative advances in vaccinology, addressing limitations of traditional vaccines through nanoscale innovations. This review summarizes recent progress in discovery, stabilization, adjuvantation, formulation, and clinical evaluation of nanovaccines. These advances have leveraged multi-omic integration and biological display platforms to target diverse antigen types, including tumor-specific neoantigens and damage-associated molecular patterns (DAMPs) for cancers, while material designs enhance antigen stability and immunogenicity through controlled epitope spacing, multivalent clustering, and pathogen-mimetic architectures. Stabilization strategies focus on optimizing physicochemical properties (size, charge, morphology) to improve lymphatic drainage, antigen retention in lymph nodes, and targeted delivery to antigen-presenting cells (APCs), with emerging biomimetic platforms demonstrating enhanced biocompatibility and tumor microenvironment modulation. Advanced adjuvantation results in immunometabolic reprogramming to amplify innate immune activation pathways such as cGAS-STING while counteracting immunosuppressive niches. In addition, evaluation technologies, including single-cell sequencing (SCS), spatial transcriptomics, and in vivo imaging, provide new insights into immune dynamics. Despite progress, challenges in scalability, biocompatibility, and clinical translation and evaluation persist. Future directions emphasize personalized vaccines, synthetic biology-driven platforms, and interdisciplinary integration to overcome existing barriers. This review highlights the potential of nanovaccines to better address disease prevention and therapy, from infectious diseases to cancer immunotherapy.