Rationalization of a Nanoparticle-Based Nicotine Nanovaccine as an Effective Next-Generation Nicotine Vaccine: A Focus on Hapten Localization

Tobacco smoking is one of the largest public health threats the world has ever faced. Even with the help of pharmacological interventions, including nicotine replacement therapy, varenicline, and bupropion, the long-term smoking cessation rate at one year is disappointingly low (10-25%). Nicotine vaccine is a promising approach for smoking cessation. A novel next-generation nanoparticle-based nicotine vaccine (NanoNicVac) was rationalized by engineering the hapten localizations in this current work. Results of mice trial suggested that NanoNicVac-LPNKN, in which nicotine haptens were conjugated to both stimulating protein and nanoparticle surface, had the highest immunogenicity and best pharmacokinetic efficacy. Specially, up to 67% of the subcutaneously dosed nicotine could be blocked from entering the brain of mice by NanoNicVac-LPNKN. In addition, histopathological study indicated that the NanoNicVac was safe and did not cause any detectable lesions to major organs of mice. Moreover, NanoNicVac has some distinguishing advantages over traditional conjugate nicotine vaccines. First, due to the fact that multiple antigens was conjugated to NanoNicVac surface, NanoNicVac had a high antigen loading capacity. Second, because of their tunable physiochemical properties and high antigen loading efficiency, NanoNicVac particles would be recognized and internalized by immune cells efficiently. Third, high bioavailability would be achieved by NanoNicVac, as it had distinguishing stability and long circulation time (caused by PEGylation). Lastly, molecular adjuvants would be easily incorporated into NanoNicVac since the PLGA core was an excellent reservoir for adjuvant encapsulation and controlled release. Overall, the highly-immunogenic NanoNicVac rationalized by modulating hapten localization can be a promising candidate for smoking cessation.

Patent Information:
Category(s):
Medical
For Information, Contact:
Rozzy Finn
Licensing Officer
Virginia Tech Intellectual Properties, Inc.
Rozzy@vt.edu
Inventors:
Chenming (mike) Zhang
Zongmin Zhao
Keywords: