title: Flagellin as carrier and adjuvant in cocaine vaccine development.
abstract: 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.
authors.affiliation: Departments of Chemistry, Integrative Structural and Computational Biology, and Immunology and Microbial Science, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Lockner
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Eubanks
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Choi
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Lively
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schlosburg
authors.forename: Karen C
authors.initials: KC
authors.lastname: Collins
authors.forename: Daniel
authors.initials: D
authors.lastname: Globisch
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Rosenfeld-Gunn
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000534:Alum Compounds / Q000737:chemistry; D000818:Animals; D001835:Body Weight; D003042:Cocaine / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005408:Flagellin / Q000737:chemistry* / Q000276:immunology; D006241:Haptens / Q000737:chemistry* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011863:Radioimmunoassay; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D006241:Haptens; D014612:Vaccines; D005408:Flagellin; C041524:aluminum sulfate; D003042:Cocaine
keywords: addiction; adjuvant; antibody; carrier protein; cocaine; conjugate; dose−response; flagellin; hapten; immunogenicity; mice; vaccine