Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

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• 作者：M. Pravetoni^a ; ^{prave001@umn.edu} ; D.E. Keyler^a ; ^b ; M.D. Raleigh^c ; A.C. Harris^a ; ^d ; M.G. LeSage^a ; ^d ; C.K. Mattson^a ; S. Pettersson^a ; P.R. Pentel^a ; ^c ; ^d ; ^{pentel@umn.edu}
• 关键词：Nicotine ; Smoke ; Cigarette ; Antibody ; Immunotherapy ; Vaccine ; Immunogenicity
• 刊名：Biochemical Pharmacology
• 出版年：2011
• 出版时间：1 May 2011
• 年：2011
• 卷：81
• 期：9
• 页码：1164-1170
• 全文大小：325 K

文摘

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 min nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a 2 h whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular mid-day smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90 % , comparable to its effect on nicotine administered i.v. Vaccination prior to 2 h smoke WBE reduced nicotine distribution to brain by 35 % . The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 h WBE was increased by 230 % in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21–25 % of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation.