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

Autor: Jacob NT; Departments of Chemistry and Immunology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Lockner JW; Departments of Chemistry and Immunology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Schlosburg JE; Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Ellis BA; Departments of Chemistry and Immunology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Eubanks LM; Departments of Chemistry and Immunology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Janda KD; Departments of Chemistry and Immunology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2016 Mar 24; Vol. 59 (6), pp. 2523-9. Date of Electronic Publication: 2016 Mar 07.
DOI: 10.1021/acs.jmedchem.5b01676
Abstrakt: 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.
Databáze: MEDLINE
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