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

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. R...

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Main Authors: Nya L. Fraleigh, Jordan D. Lewicky, Alexandrine L. Martel, Francisco Diaz-Mitoma, Hoang-Thanh Le
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/2/118
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author Nya L. Fraleigh
Jordan D. Lewicky
Alexandrine L. Martel
Francisco Diaz-Mitoma
Hoang-Thanh Le
author_facet Nya L. Fraleigh
Jordan D. Lewicky
Alexandrine L. Martel
Francisco Diaz-Mitoma
Hoang-Thanh Le
author_sort Nya L. Fraleigh
collection DOAJ
description 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.
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spelling doaj.art-19ded2b61e2047dbbf45f99172fcad5e2023-12-03T12:11:16ZengMDPI AGVaccines2076-393X2021-02-019211810.3390/vaccines9020118Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine VaccineNya L. Fraleigh0Jordan D. Lewicky1Alexandrine L. Martel2Francisco Diaz-Mitoma3Hoang-Thanh Le4Department of Research, Health Sciences North Research Institute (HSNRI), 56 Walford Road, Sudbury, ON P3E 2H3, CanadaDepartment of Research, Health Sciences North Research Institute (HSNRI), 56 Walford Road, Sudbury, ON P3E 2H3, CanadaDepartment of Research, Health Sciences North Research Institute (HSNRI), 56 Walford Road, Sudbury, ON P3E 2H3, CanadaDepartment of Chemistry & Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, CanadaDepartment of Research, Health Sciences North Research Institute (HSNRI), 56 Walford Road, Sudbury, ON P3E 2H3, CanadaTobacco 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.https://www.mdpi.com/2076-393X/9/2/118nicotine vaccinemucosalintranasalnicotine distributionnicotine analysis method
spellingShingle Nya L. Fraleigh
Jordan D. Lewicky
Alexandrine L. Martel
Francisco Diaz-Mitoma
Hoang-Thanh Le
Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine
Vaccines
nicotine vaccine
mucosal
intranasal
nicotine distribution
nicotine analysis method
title Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine
title_full Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine
title_fullStr Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine
title_full_unstemmed Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine
title_short Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine
title_sort assessing neutralized nicotine distribution using mice vaccinated with the mucosal conjugate nicotine vaccine
topic nicotine vaccine
mucosal
intranasal
nicotine distribution
nicotine analysis method
url https://www.mdpi.com/2076-393X/9/2/118
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