Skip to main content
Grant Details

Grant Number: 5R01CA102259-03 Interpret this number
Primary Investigator: Sanderson, Sam
Organization: University Of Nebraska Medical Center
Project Title: Development of Peptide-Based Vaccines to Nicotine
Fiscal Year: 2006
Back to top


Abstract

DESCRIPTION (provided by applicant): The primary objective of this project is to develop an effective, peptide-based nicotine vaccine for use in humans capable of inducing a robust, nicotine-specific antibody (Ab) response with little or no inflammatory side effects. This will be accomplished by vaccine designs in which conformationally biased, response-selective agonists of C5a (YSFKPMPLaR and YSFKDMP(MeL)a) are used as molecular adjuvants and a nicotine hapten is used as the target antigen (Ag). The ability of such molecular adjuvant-containing vaccines to induce an anti-nicotine immune response will be assessed by two general methods. The first is to characterize the molecular and cellular mechanisms by which the molecular adjuvants engage C5a receptor (C5aR)-bearing antigen presenting cells (APC) to enhance the APCs' ability to process and present the nicotine Ag. The second is to vaccinate rats with molecular adjuvant-containing nicotine vaccines in the absence of added adjuvant and demonstrate the presence of nicotine-specific Abs in immune sera/tissues and an attenuation of nicotine-induced behavioral effects in two well-established rat models of nicotine dependence. Validation of these peptide-based, molecular adjuvant-containing nicotine vaccines represents the first step toward realization of the broad objective sought by this project, which is to use vaccination to nicotine with such vaccines as a standard therapeutic regimen for smoking cessation and maintenance of long term compliance. The first steps toward this broad objective will be taken with the following specific aims: 1) To characterize the cellular and molecular mechanisms by which the molecular adjuvants YSFKPMPLaR and YSFKDMP(MeL)aR engage C5aR-bearing human APCs such that these cells are activated and their Ag processing/presenting capacity is enhanced. 2) To test YSFKPMPLaR- and YSFKDMP(MeL)aR-containing nicotine vaccines for their ability to induce anti-nicotine immune responses in rats without the use of added adjuvants, and 3) To test whether vaccination with YSFKPMPLaR- and YSFKDMP(MeL)aR-containing vaccines attenuates the behavioral effects of nicotine in well-characterized rat models of nicotine dependence.

Back to top


Publications

Error Notice

If you are accessing this page during weekend or evening hours, the database may currently be offline for maintenance and should operational within a few hours. Otherwise, we have been notified of this error and will be addressing it immediately.

Please contact us if this error persists.

We apologize for the inconvenience.
- The DCCPS Team.


Back to Top