期刊
MOLECULAR PHARMACEUTICS
卷 12, 期 2, 页码 653-662出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp500520r
关键词
addiction; adjuvant; antibody; carrier protein; cocaine; conjugate; dose-response; flagellin; hapten; immunogenicity; mice; vaccine
资金
- Amgen
- Skaggs Institute for Chemical Biology
- National Institute on Drug Abuse [DA08590]
- National Institute of Allergy and Infectious Diseases [AI042266]
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.
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