Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development

Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has bee...

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Veröffentlicht in:Journal of medicinal chemistry 2016-03, Vol.59 (6), p.2523-2529
Hauptverfasser: Jacob, Nicholas T, Lockner, Jonathan W, Schlosburg, Joel E, Ellis, Beverly A, Eubanks, Lisa M, Janda, Kim D
Format: Artikel
Sprache:eng
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Zusammenfassung:Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has been to elicit a sufficiently high antibody concentration to curb nicotine distribution to the brain. Herein, we detail investigations into a new hapten design, which was able to elicit an antibody response of significantly higher specificity for nicotine. We also explore the use of a mutant flagellin carrier protein with adjuvanting properties. These studies underlie the feasibility of improvement in antinicotine vaccine formulations to move toward clinical efficacy.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.5b01676