Suppression of Nicotine-Induced Pathophysiology by an Adenovirus Hexon-Based Anti-Nicotine Vaccine.

Suppression of Nicotine-induced Pathophysiology by an Adenovirus Hexon-based Anti-nicotine Vaccine.

Hum Gene Ther. 2013 Apr 23;
Rosenberg J, De B, Hicks M, Janda K, Kaminsky S, Worgall S, Crystal R

Despite anti-smoking campaigns, cigarette smoking remains a pervasive addiction with significant societal impact, accounting for 1 of every 5 deaths. Smoking cessation therapies to help smokers quit are ineffective with a high recidivism rate. With the knowledge that nicotine is the principal addictive compound of cigarettes, we have developed an anti-smoking vaccine based on the highly immunogenic properties of the hexon protein purified from the serotype 5 adenovirus (Ad) capsid. We hypothesized that an effective anti-nicotine vaccine could be based on coupling the nicotine hapten AM1 to purified Ad hexon protein. To assess this, AM1 was conjugated to hexon purified from serotype 5 Ad to produce the “HexonAM1” vaccine. C57Bl/6 mice were sensitized by 10 daily nicotine administrations (0.5 mg/kg, subcutaneous) to render the mice addicted to nicotine. Control groups were sensitized to PBS. The mice were then im-munized with HexonAM1 (4 µg, intramuscular) at 0, 3, and 6 wk. By 6 wk, the HexonAM1-vaccinated mice had serum anti-nicotine antibody titers of 1.1 x 106 ± 7.6 x 104. To demonstrate that these high anti-nicotine titers were sufficient to suppress the effects of nicotine, HexonAM1-vaccinated mice were evaluated for nicotine-induced hypoactive behavior with nicotine chal-lenges (0.5 mg/kg wt) over 5 wk. In all challenges, the HexonAM1-vaccinated mice behaved similarly to that of PBS-challenged naive mice. These data demonstrate that a vaccine comprised of a nicotine analog coupled to Ad hexon can evoke high level anti-nicotine antibodies sufficient to inhibit nicotine-induced behavior. The HexonAM1 vaccine represents a platform paradigm for vaccines against small molecules. HubMed – addiction



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