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.
Highlights
IntroductionSmoking tobacco increases risks associated with cancer, respiratory and cardiovascular diseases but results in a substantial social and economic burden that in Canada is responsible for 18% of deaths and over CAD 16 billion of direct and indirect costs [2]
We have previously demonstrated that utilizing a heterologously (intramuscular (IM)/intranasal (IN)) administered, mucosally directed nicotine vaccine induced robust mucosal and systemic antibodies directed towards nicotine, resulting in two levels of protection [11]
The core of this conjugate nicotine vaccine platform is composed of a bacterial-derived adjuvant (BDA) from either N. meningitides or V. cholerae and both have been used as part of effective human vaccines [11,12,19,20,21,22]
Summary
Smoking tobacco increases risks associated with cancer, respiratory and cardiovascular diseases but results in a substantial social and economic burden that in Canada is responsible for 18% of deaths and over CAD 16 billion of direct and indirect costs [2]. Smoking cessation aides, such as nicotine replacement products and pharmacotherapeutics, are readily available to help those who wish to quit smoking, success rates remain low with a high risk of relapse [3]. These vaccines continue to rely on parenteral administration, limiting the availability of the antinicotine antibodies to the systemic circulation, which alone may be unable to efficiently capture nicotine
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