Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine

Abstract

Tobacco smoking continues to be a global epidemic and the leading preventable cause of cancer and cardiovascular disease. Nicotine vaccines have been investigated as an alternative to currently available smoking cessation strategies as a means to increase rates of success and long-term abstinence. Recently, we demonstrated that a mucosal nicotine vaccine was able to induce robust mucosal and systemic antibodies when delivered heterologously using intranasal and intramuscular routes. Herein, we investigated the neutralization ability of the anti-nicotine antibodies using both intranasal and intracardiac nicotine challenges. Combining the extraction of lyophilized organ samples with RP-HPLC methods, we were able to recover between 47% and 56% of the nicotine administered from the blood, brain, heart, and lungs up to 10 min after challenge, suggesting that the interaction of the antibodies with nicotine forms a stable complex independently of the route of vaccination or challenge. Although both challenge routes can be used for assessing systemic antibodies, only the intranasal administration of nicotine, which is more physiologically similar to the inhalation of nicotine, permitted the crucial interaction of nicotine with the mucosal antibodies generated using the heterologous vaccination route. Notably, these results were obtained 6 months after the final vaccination, demonstrating stable mucosal and systemic antibody responses.

Vaccines to Treat Substance Use Disorders: Current Status and Future Directions

“…Indeed, antagonizing the effects of nicotine has shown promise in conjunction with varenicline, considered the most effective smoking cessation treatment available. Animal studies, especially in rats across laboratories and across specific vaccine compounds, have indicated that immunization leads to reduced nicotine penetration into the brain and diminished behavioral responses to nicotine, including locomotor effects [ 83 , 84 ]. However, the limited published human studies exploring various nicotine vaccines have not yet provided substantial evidence supporting vaccine efficacy as a treatment for nicotine dependence.…”