期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 3, 期 1, 页码 137-146出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S1567-5769(02)00260-6
关键词
conformationally biased c5a agonist; molecular adjuvant; peptide-based nicotine vaccine
资金
- NIDA NIH HHS [DA 11893] Funding Source: Medline
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA011893] Funding Source: NIH RePORTER
This paper describes the synthesis of a nicotine hapten (Nic) that possesses a carboxyl sidearm functional group allowing for conjugation to a peptide via amide bond formation. Nic was attached to the N-terminal amino group of a 19-residue peptide composed of a conformationally biased agonist of human C5a (YSFKPMPLaR), which is used as a molecular adjuvant and a B cell epitope of human MUC1 glycoprotein (YKQGGFLGL) to yield a peptide-based nicotine vaccine, NicYKQGGFL-GLYSFKPMPLaR. Rats immunized with this vaccine were significantly less sensitive to behavioral effects (a Pavlovian discrimination task) induced by their exposure to high concentrations of nicotine (0.4 mg/kg) relative to their non-vaccinated counterparts. The attenuation of these nicotine-induced behavioral effects emanated from the presence of nicotine-specific antibodies (Abs) that were present in the sera of vaccinated rats even after their repeated exposure to high concentrations of nicotine during the time required to perform the behavioral assays. These results suggest that immunization with NicYKQGGFLGLYSFKPMPLaR in the absence of adjuvant is an effective means of inducing a nicotine-specific Ab response, which is capable of attenuating nicotine-induced behavioral/psychoactive effects. (C) 2002 Elsevier Science B.V. All rights reserved.
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