Engineered polysaccharides for controlling innate and adaptive immune responses

Therapeutic interventions can be designed by exploiting the immune system’s ability to initiate specific responses to various stimuli. However, specific T cell activation, which is a key target for vaccines and immunotherapies, remains challenging. Polysaccharides derived from microbial cell walls are promising immunomodulators that interact with pathogen-recognition receptors (PRRs) on dendritic cells and macrophages, triggering robust immune responses for modulating T cell function and activating effector or regulatory pathways. In this Review, we discuss the role of polysaccharides as pathogen-associated molecular patterns (PAMPs) recognized by PRRs and their immunomodulatory potential for biomedical applications. We examine the engineering aspects of polysaccharides, investigating their potential in vaccine, immunoadjuvant, immune-modulation and drug-delivery applications and highlighting their immune-activating or immune-regulatory functions. We also explore how trained immunity can be induced by polysaccharides to trigger immune responsiveness upon re-encountering pathogens. By leveraging materials engineering principles, polysaccharides can offer a platform for effective vaccines and immunotherapies against autoimmune and other diseases. Polysaccharides possess immune-activating or immune-regulatory functions and can thus be applied as immunomodulators. This Review discusses engineering approaches for the design of polysaccharides for vaccine, immunoadjuvant, immune-modulation and drug-delivery applications.