Tobacco smoke is the primary cause of lung cancer, cardiovascular disease and premature death, with nearly 5 million people dying each year. Treatments that prevent smoking will have a major impact on global health and are attractive products for commercial development. Nicotine vaccines and antibodies represent an important strategy for preventing nicotine from reaching the brain, although current clinical-stage vaccines are ineffective and for most people the antibody response is weak and short-lived. The challenge of inducing long- lasting antibodies titers requires a better method for presenting nicotine to the immune system. We hypothesize that targeted nicotine delivery to dendritic cells using agonistic mAbs to CD40 combined with a TLR4-based adjuvant will stimulate a superior antibody response. We will modify the rat anti-mouse CD40 mAb 1C10 for studies in mice and optimize its conjugation with derivatized nicotine. Mice will be vaccinated with ?CD40nic formulated with the TLR4-activating adjuvant GLA-SE. Anti-nicotine antibody titers will be benchmarked against mice vaccinated with a traditional vaccine, nicotine-KLH + alum. Vaccine potency will be determined using quantitative measures of antibody function including nicotine sequestration in blood and prevention of a nicotine abstinence response. Phase I SBIR funding will establish proof-of-concept in a relevant model and provide the justification for subsequent IND-enabling studies that will bring an innovative vaccine for smoking cessation into the clinic.

Public Health Relevance

Tobacco smoke is the primary cause of lung cancer, cardiovascular disease and premature death. There is a strong unmet need for an effective aid to smoking cessation. To halt the addictive effects of nicotine and increase the success rate for smoking cessation, we have designed a novel vaccine that will prevent nicotine from crossing the blood-brain barrier.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43DA033845-01
Application #
8315224
Study Section
Special Emphasis Panel (ZRG1-IMM-G (10))
Program Officer
Park, Moo Kwang
Project Start
2012-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$151,451
Indirect Cost
Name
Tria Bioscience Corporation
Department
Type
DUNS #
831016907
City
Seattle
State
WA
Country
United States
Zip Code
98102