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Modular complement assemblies for mitigating inflammatory conditions.

Kelly M Hainline1, Lucas S Shores1, Nicole L Votaw1

  • 1Biomedical Engineering Department, Duke University, Durham, NC 27708.

Proceedings of the National Academy of Sciences of the United States of America
|April 20, 2021
PubMed
Summary
This summary is machine-generated.

Researchers developed supramolecular nanofibers displaying complement protein C3dg for active immunotherapy. These C3dg assemblies show therapeutic potential, acting as molecular adjuvants to enhance immune responses and treat inflammatory diseases.

Keywords:
active immunotherapyimmune engineeringimmunoengineeringself-assemblyvaccine

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Area of Science:

  • Immunology
  • Biotechnology
  • Materials Science

Background:

  • Complement protein C3dg links innate and adaptive immunity, showing potential as a molecular adjuvant.
  • Current limitations in C3dg adjuvant use stem from difficulties in assembling multiple copies into vaccine platforms.

Purpose of the Study:

  • To develop a strategy for assembling C3dg into supramolecular nanofibers for use as therapeutic active immunotherapies.
  • To investigate the efficacy of C3dg-based nanofiber assemblies in treating chronic inflammatory diseases.

Main Methods:

  • Utilized β-tail fusion tags to assemble C3dg into supramolecular nanofibers with controlled composition.
  • Investigated assemblies containing C3dg, TNF B cell epitopes, and PADRE T cell epitope in immunization models.
  • Evaluated therapeutic efficacy in a TNF-mediated inflammation model and an imiquimod-induced psoriasis model.

Main Results:

  • Nanofiber assemblies induced strong antibody responses against TNF and C3dg.
  • Prophylactic immunization with C3dg nanofibers improved protection in a lethal inflammation model.
  • C3dg-adjuvanted nanofibers demonstrated efficacy comparable to anti-TNF monoclonal antibodies in a psoriasis model.
  • Supramolecular C3dg alone showed therapeutic benefits, potentially by expanding regulatory T cells.

Conclusions:

  • Molecular assemblies displaying C3dg are a promising strategy for active immunotherapy.
  • Supramolecular C3dg exhibits intrinsic therapeutic properties for inflammatory conditions.
  • Further development of C3dg-based molecular assemblies is warranted for treating chronic inflammatory diseases.