Tobacco addiction is the single largest cause of cancer and heart disease resulting in 6 million deaths a year world-wide. Vaccines that induce anti-nicotine antibodies and prevent nicotine from crossing the blood brain barrier are an important strategy for smoking cessation, although the concept is not yet proven in humans. Nicotine is non-immunogenic due to its small size and must be conjugated to a larger carrier protein. Thus, the challenge of inducing functional nicotine antibodies requires better methods for presenting nicotine antigens to the immune system. To accomplish this, we have invented a synthetic TriCoil carrier with a high density of nicotine haptens, which is a key determinant of immunogenicity, and a series of CD4 T cell epitopes for regulating B cell help. Proof-of-concept experiments demonstrated that the formulation of this vaccine with the clinical- stage adjuvant GLA-SE, induced a high affinity antibody response in mice that was 10-fold more effective than a conventional nicotine vaccine. We hypothesize that a TriCoil-based vaccine adjuvanted with GLA-SE will activate a larger repertoire of B and T cells in smokers and significantly increase functional anti-nicotine Ab concentrations. To advance this project to the clinic we will complete 2 go/no-go decision points. First, we will down-select a trivalent vaccine in mice with optimized B- and T cell epitopes, and then during year 2, test for efficacy using a gold standard behavioral model in rats. Achievement of this first goal will prompt a study in non-human primates that will establish vaccine superiority relative to a NIC7 mimetic vaccine, which is currently being tested in the clinic. Reaching this second goal during year 3 will trigger initiatin of cGMP manufacturing, GLP-tox safety testing, and submission of an IND during year 5. Successful completion of this project will result in a promising new vaccine for smoking cessation that has several distinct advantages including a structurally- defined hapten carrier, a more potent adjuvant, and a superior manufacturing process for scale-up and commercialization.

Public Health Relevance

The health risks and economic burden associated with smoking are clear and undeniable. We are developing a vaccine for smoking cessation that stimulates anti-nicotine antibodies and prevents this drug from crossing the blood brain barrier, thereby neutralizing the addictive properties associated with tobacco products.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
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Special Emphasis Panel (ZDA1)
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Kline, Richard
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Tria Bioscience Corporation
United States
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