. Over the past quarter century, the concept of "therapeutic vaccines" has broadened from the initial, narrow meaning of a immunization against a microbial pathogen to the current, broad meaning of any treatment that can stimulate a beneficial immune response. As a result, scientists and physicians are now trying develop "vaccines" against such esoteric targets as tumors and drugs of addiction. The latter category includes vaccines against nicotine. The logic of a nicotine vaccine is that circulating anti- nicotine antibodies will intercept nicotine in the blood before it reaches the brain where its physiologic target resides. Already, pre-clinical and clinical trial data support the concept that nicotine vaccines can reduce the physiologic effects of smoking and reduce the likelihood of regaining an addiction to nicotine after smoking cessation. In parallel with the development of nicotine vaccines, there have been advances in the delivery vehicles for vaccines. Among these advances is the recognition that vaccines delivered as small particles ("nanoparticles" ranging from 40 to 100 billionths of a meter in diameter) and vaccines delivered by viruses are more efficacious than vaccines delivered by soluble proteins. A central concept in this proposal is that viruses, and in particular, adenoviruses, represent an especially effective form of nanoparticle vaccines due to their size (80 billionths of a meter) and their ability to interact with the cell surface as part of their infection cycle. This proposal seeks to combine the efficacy of adenovirus-based vaccines with the importance of nicotine as a target and will test the hypothesis that direct covalent conjugation of nicotine to the adenovirus caspid will result in a highly effective vaccine that is capable of generating therapeutically relevant levels of anti-nicotine antibodies.

Public Health Relevance

. Recent studies suggest that vaccines are more effective if they are delivered as tiny particles (nanoparticles) instead of soluble proteins. The present study will test whether adenovirus, a nanoparticle that is approximately 80 billionths of a meter wide, can be used to create a new, even more effective class of nanoparticle vaccines. Studies will focus on a vaccine against nicotine, which may help smokers to quit smoking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA025305-05
Application #
8465850
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Singh, Hari
Project Start
2009-08-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$350,548
Indirect Cost
$143,123
Name
Weill Medical College of Cornell University
Department
Genetics
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Rosenberg, Jonathan B; De, Bishnu P; Hicks, Martin J et al. (2013) Suppression of nicotine-induced pathophysiology by an adenovirus hexon-based antinicotine vaccine. Hum Gene Ther 24:595-603
De, Bishnu P; Pagovich, Odelya E; Hicks, Martin J et al. (2013) Disrupted adenovirus-based vaccines against small addictive molecules circumvent anti-adenovirus immunity. Hum Gene Ther 24:58-66
Wee, Sunmee; Hicks, Martin J; De, Bishnu P et al. (2012) Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects. Neuropsychopharmacology 37:1083-91
Rosenberg, Jonathan B; Hicks, Martin J; De, Bishnu P et al. (2012) AAVrh.10-mediated expression of an anti-cocaine antibody mediates persistent passive immunization that suppresses cocaine-induced behavior. Hum Gene Ther 23:451-9
Hicks, Martin J; De, Bishnu P; Rosenberg, Jonathan B et al. (2011) Cocaine analog coupled to disrupted adenovirus: a vaccine strategy to evoke high-titer immunity against addictive drugs. Mol Ther 19:612-9
Moreno, Amira Y; Janda, Kim D (2011) Current challenges for the creation of effective vaccines against drugs of abuse. Expert Rev Vaccines 10:1637-9