Details

Autor(en) / Beteiligte

• 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

Titel

Flagellin as Carrier and Adjuvant in Cocaine Vaccine Development

Ist Teil von

• Molecular pharmaceutics, 2015-02, Vol.12 (2), p.653-662

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.