Protein-glycan engineering in vaccine design: merging immune mechanisms with biotechnological innovation

Glycans are critical regulators of immune recognition, influencing pathogen detection and immune modulation. Despite their potential in vaccine design, challenges, such as glycan heterogeneity and immune evasion, persist. Recent advances in protein-glycan engineering, spanning clustered regularly interspaced short palindromic repeats (CRISPR)-based glycoediting, synthetic biology, and glycan-modified nanoparticles (NPs), are now enabling precise control of glycan structures to enhance antigen presentation and immune activation. These innovations improve antigen stability, optimize immune responses, and expand vaccine targets to emerging pathogens, tumors, and autoimmune disorders. Computational tools further refine glycan engineering for rational vaccine design. In this review, by providing essential immunological context on glycan-mediated mechanisms in infection, cancer, and autoimmunity, we highlight how integrating cutting-edge biotechnologies with protein-glycan research is redefining vaccine efficacy and informing the development of next-generation glycoengineered vaccines.