Activation of innate immune responses in a pathogen-mimicking manner by amphiphilic polyanhydride nanoparticle adjuvants

Latrisha K. Petersen, Amanda E. Ramer-Tait, Scott R. Broderick, Chang Sun Kong, Bret D. Ulery, Krishna Rajan, Michael J. Wannemuehler, Balaji Narasimhan

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Techniques in materials design, immunophenotyping, and informatics can be valuable tools for using a molecular based approach to design vaccine adjuvants capable of inducing protective immunity that mimics a natural infection but without the toxic side effects. This work describes the molecular design of amphiphilic polyanhydride nanoparticles that activate antigen presenting cells in a pathogen-mimicking manner. Biodegradable polyanhydrides are well suited as vaccine delivery vehicles due to their adjuvant-like ability to: 1) enhance the immune response, 2) preserve protein structure, and 3) control protein release. The results of these studies indicate that amphiphilic nanoparticles possess pathogen-mimicking properties as evidenced by their ability to activate dendritic cells similarly to LPS. Specific molecular descriptors responsible for this behavior were identified using informatics analyses, including the number of backbone oxygen moieties, percent of hydroxyl end groups, polymer hydrophobicity, and number of alkyl ethers. Additional findings from this work suggest that the molecular characteristics mediating APC activation are not limited to hydrophobicity but vary in complexity (e.g., presentation of oxygen-rich molecular patterns to cells) and elicit unique patterns of cellular activation. The approach outlined herein demonstrates the ability to rationally design pathogen-mimicking nanoparticle adjuvants for use in next-generation vaccines against emerging and re-emerging diseases.

Original languageEnglish (US)
Pages (from-to)6815-6822
Number of pages8
JournalBiomaterials
Volume32
Issue number28
DOIs
StatePublished - Oct 1 2011

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Keywords

  • Combinatorial
  • High throughput
  • Nanoparticles
  • Polyanhydrides
  • Vaccine adjuvants

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Petersen, L. K., Ramer-Tait, A. E., Broderick, S. R., Kong, C. S., Ulery, B. D., Rajan, K., Wannemuehler, M. J., & Narasimhan, B. (2011). Activation of innate immune responses in a pathogen-mimicking manner by amphiphilic polyanhydride nanoparticle adjuvants. Biomaterials, 32(28), 6815-6822. https://doi.org/10.1016/j.biomaterials.2011.05.063