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  • Review Article
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Engineered polysaccharides for controlling innate and adaptive immune responses

Abstract

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.

Key points

  • Current subunit vaccines often lack immunogenicity compared to traditional whole-microbe vaccines, requiring immune modulators to enhance antigen immunogenicity and efficacy.

  • Polysaccharides can serve as pathogen-associated molecular patterns (PAMPs) that interact with pathogen-recognition receptors (PRRs) on dendritic cells and macrophages, triggering robust immune responses.

  • The immunological activities of polysaccharides depend on their origin, type and structure, and can thus be optimized for their rational design.

  • Engineered polysaccharides, with diverse structural and immunological characteristics, offer a versatile platform for biomedical applications, demonstrating potential in immunotherapy against autoimmunity, vaccine delivery and induction of trained immunity.

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Fig. 1: Targeting pathogen-recognition receptors on dendritic cells can shape specific T cell-mediated responses.
Fig. 2: The biological and immunological roles of macrophages.
Fig. 3: Engineering the immunogenicity of polysaccharides.
Fig. 4: Trained immunity is regulated by metabolic and epigenetic reprogramming of innate immune cells.

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Acknowledgements

This work was supported in part by the NIH (R01DE030691, R01DK125087, R01CA271799), National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (2022R1A2C1006643, RS-2023-00212229), the Institute of Civil Military Technology Cooperation funded by the Defense Acquisition Program Administration and the Ministry of Trade, Industry and Energy of Korean government (22-CM-17). A.K. is supported by a predoctoral fellowship from the Cellular Biotechnology Training Program (T32GM008353).

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S.S. outlined the manuscript. J.N., A.K., K.K., J.J.M. and S.S. discussed content, researched data and wrote the manuscript. J.H.M., J.B. and M.P. helped with the figures and prepared the tables. All authors reviewed and edited the manuscript.

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Correspondence to James J. Moon or Sejin Son.

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Nam, J., Kim, A., Kim, K. et al. Engineered polysaccharides for controlling innate and adaptive immune responses. Nat Rev Bioeng (2024). https://doi.org/10.1038/s44222-024-00193-2

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