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Flagellin as carrier and adjuvant in cocaine vaccine development

Molecular Pharmaceutics, ISSN: 1543-8392, Vol: 12, Issue: 2, Page: 653-662
2015
  • 43
    Citations
  • 0
    Usage
  • 54
    Captures
  • 1
    Mentions
  • 12
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    43
  • Captures
    54
  • Mentions
    1
    • News Mentions
      1
      • News
        1
  • Social Media
    12
    • Shares, Likes & Comments
      12
      • Facebook
        12

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Article Description

Cocaine abuse is problematic, directly and indirectly impacting the lives of millions, and yet existing therapies are inadequate and usually ineffective. A cocaine vaccine would be a promising alternative therapeutic option, but efficacy is hampered by variable production of anticocaine antibodies. Thus, new tactics and strategies for boosting cocaine vaccine immunogenicity must be explored. Flagellin is a bacterial protein that stimulates the innate immune response via binding to extracellular Toll-like receptor 5 (TLR5) and also via interaction with intracellular NOD-like receptor C4 (NLRC4), leading to production of pro-inflammatory cytokines. Reasoning that flagellin could serve as both carrier and adjuvant, we modified recombinant flagellin protein to display a cocaine hapten termed GNE. The resulting conjugates exhibited dose-dependent stimulation of anti-GNE antibody production. Moreover, when adjuvanted with alum, but not with liposomal MPLA, GNE-FliC was found to be better than our benchmark GNE-KLH. This work represents a new avenue for exploration in the use of hapten-flagellin conjugates to elicit antihapten immune responses.

Bibliographic Details

Lockner, Jonathan W; Eubanks, Lisa M; Choi, Jennifer L; Lively, Jenny M; Schlosburg, Joel E; Collins, Karen C; Globisch, Daniel; Rosenfeld-Gunn, Robin J; Wilson, Ian A; Janda, Kim D

American Chemical Society (ACS)

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics

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