Research Funded for DNA Vaccine to Create Nicotine Immunity

Hand holding cigarette (NIMH) — (National Institute of Mental Health)

Researchers at Arizona State University in Tempe are investigating the ability of human DNA, assembled into nanoscale particles, to help people develop an immunity to nicotine. The project is funded by a three-year $3.3 million grant from National Institute of Drug Abuse, part of National Institutes of Health, and led by Arizona State immunologist Yung Chang.

According to National Institute of Drug Abuse, most cigarette smokers identify tobacco as harmful and express a desire to quit, but more than 85 percent of those who try to quit on their own relapse, often within a week. Nicotine from tobacco activates pleasure pathways in the brain by increasing levels of dopamine in the reward circuits. In addition, smoking sends nicotine quickly to the brain, but the pleasure effects of nicotine dissipate quickly, creating repeated cravings and requiring continued doses of nicotine.

Chang and colleagues at Arizona State’s Biodesign Institute are taking a different approach to breaking the hold of nicotine on the body, by harnessing the body’s immune system to stimulate antibodies that bind with nicotine and keep it from reaching the brain’s reward circuits. However, efforts so far to generate antibodies that bind to nicotine, penetrate cells, and induce immunity produced mixed results.

In this new project, Chung aims to adapt work by Bioscience Institute colleague Hao Yan on the design of nanoparticles made of DNA. The researchers plan to construct three types of DNA platforms for configuring the vaccine’s components that promote an immune response, yet are safe and effective. The components include:

– Minimal amounts of nicotine molecules to bind with the nicotine in tobacco smoke

– An additive called an adjuvant that promotes a stronger response from the body’s B-cells, white blood cells that secrete antibodies

– Antigens that bind to antibodies and attract helper T cells, another form of white blood cell in the immune system that works with B-cells

The researchers expect the design of the platform and configuration of the components to be crucial to the success of the project and tricky to accomplish. Two of the platforms tested will be simpler in design with scaffolds made of 8 or 12 branches, while the third structure is a tetrahedron — a 3-D structure with four triangular faces — having 36 discreet positions for the components.

In addition to testing three alternative structures, the researchers expect to test different combinations of components in the lab and with animal models. The goal of the team is to identify two or three vaccine candidates for subsequent clinical trials and eventual submission for regulatory approval.

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