The use of nanolipoprotein particles to enhance the immunostimulatory properties of innate immune agonists against lethal influenza challenge

Dina R. Weilhammer, Craig D. Blanchette, Nicholas O Fischer, Shabnam Alam, Gabriela G. Loots, Michele Corzett, Cynthia Thomas, Cheri Lychak, Alexis D. Dunkle, Joyce J. Ruitenberg, Smita A. Ghanekar, Andrea J. Sant, Amy Rasley

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Recent studies have demonstrated that therapies targeting the innate immune system have the potential to provide transient, non-specific protection from a variety of infectious organisms; however, the potential of enhancing the efficacy of such treatments using nano-scale delivery platforms requires more in depth evaluation. As such, we employed a nanolipoprotein (NLP) platform to enhance the efficacy of innate immune agonists. Here, we demonstrate that the synthetic Toll-like receptor (TLR) agonists monophosphoryl lipid A (MPLA) and CpG oligodeoxynucleotides (CpG) can be readily incorporated into NLPs. Conjugation of MPLA and CpG to NLPs (MPLA:NLP and CpG:NLP, respectively) significantly enhanced their immunostimulatory profiles both invitro and invivo compared to administration of agonists alone, as evidenced by significant increases in cytokine production, cell surface expression of activation markers, and upregulation of immunoregulatory genes. Importantly, enhancement of cytokine production by agonist conjugation to NLPs was also observed in primary human dendritic cells. Furthermore, BALB/c mice pretreated with CpG:NLP constructs survived a lethal influenza challenge whereas pretreatment with CpG alone had no effect on survival.

Original languageEnglish (US)
Pages (from-to)10305-10318
Number of pages14
JournalBiomaterials
Volume34
Issue number38
DOIs
StatePublished - Dec 2013
Externally publishedYes

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Keywords

  • Antimicrobial
  • Drug delivery
  • Immunomodulation
  • Immunostimulation
  • Nanoparticle

ASJC Scopus subject areas

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

Cite this

Weilhammer, D. R., Blanchette, C. D., Fischer, N. O., Alam, S., Loots, G. G., Corzett, M., Thomas, C., Lychak, C., Dunkle, A. D., Ruitenberg, J. J., Ghanekar, S. A., Sant, A. J., & Rasley, A. (2013). The use of nanolipoprotein particles to enhance the immunostimulatory properties of innate immune agonists against lethal influenza challenge. Biomaterials, 34(38), 10305-10318. https://doi.org/10.1016/j.biomaterials.2013.09.038