Through multidisciplinary interactions and collaborations involving immunologists, organic chemists, nanostructural chemists and neuroscientists, we will employ a bottom-up strategy to engineer nicotine hapten, T helper cell peptides and adjuvant onto self-assembling DNA nanoscaffolds in a controllable fashion to induce T-cell dependent anti-nicotine antibody responses. Robust and versatile synthesis and assembly of various antigenic components onto DNA-nanoscaffolds along with step-wise screening afford opportunities to identify "optimal combinations and configurations" of the nanovaccine for the induction of strong, anti-nicotine antibody responses, leading to production of high titer and high affinity anti-nicotine antibodies for treatment of nicotine dependence. It is conceivable that this approach can be readily extended to the development of any vaccines, including those targeting drugs of abuse, microbial pathogens and tumor antigens. Thus, the project represents a proof-of-concept investigation of a new and unconventional technology in vaccine construction.

Public Health Relevance

We propose to develop novel DNA nanovaccines against nicotine. Through rational design and step-wise screenings, we aim to create effective nicotine vaccines to treat nicotine dependence toward a longer-term goal of reducing tobacco-related diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA030045-02
Application #
8225234
Study Section
Special Emphasis Panel (ZDA1-SXC-E (07))
Program Officer
Chiang, Nora
Project Start
2011-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$174,361
Indirect Cost
$41,358
Name
Arizona State University-Tempe Campus
Department
Other Health Professions
Type
Organized Research Units
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Wu, Jie; Lukas, Ronald J (2011) Naturally-expressed nicotinic acetylcholine receptor subtypes. Biochem Pharmacol 82:800-7