Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development
Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has bee...
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| Veröffentlicht in: | Journal of medicinal chemistry 2016-03, Vol.59 (6), p.2523-2529 |
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| container_end_page | 2529 |
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| container_issue | 6 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 59 |
| creator | Jacob, Nicholas T Lockner, Jonathan W Schlosburg, Joel E Ellis, Beverly A Eubanks, Lisa M Janda, Kim D |
| description | Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has been to elicit a sufficiently high antibody concentration to curb nicotine distribution to the brain. Herein, we detail investigations into a new hapten design, which was able to elicit an antibody response of significantly higher specificity for nicotine. We also explore the use of a mutant flagellin carrier protein with adjuvanting properties. These studies underlie the feasibility of improvement in antinicotine vaccine formulations to move toward clinical efficacy. |
| doi_str_mv | 10.1021/acs.jmedchem.5b01676 |
| format | Article |
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Med. Chem</addtitle><description>Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has been to elicit a sufficiently high antibody concentration to curb nicotine distribution to the brain. Herein, we detail investigations into a new hapten design, which was able to elicit an antibody response of significantly higher specificity for nicotine. We also explore the use of a mutant flagellin carrier protein with adjuvanting properties. These studies underlie the feasibility of improvement in antinicotine vaccine formulations to move toward clinical efficacy.</description><subject>Animals</subject><subject>Antibody Formation - drug effects</subject><subject>Drug Carriers</subject><subject>Flagellin - chemistry</subject><subject>Haptens</subject><subject>Hypothermia - chemically induced</subject><subject>Hypothermia - prevention & control</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nicotine - analogs & derivatives</subject><subject>Nicotine - chemistry</subject><subject>Nicotine - immunology</subject><subject>Pain Measurement - drug effects</subject><subject>Serum Albumin, Bovine - chemistry</subject><subject>Serum Albumin, Bovine - immunology</subject><subject>Smoking Cessation</subject><subject>Structure-Activity Relationship</subject><subject>Vaccines - chemical synthesis</subject><subject>Vaccines - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1OwzAQRi0EoqVwA4RygYSx4zjJsiqFVqpgQ9lGtmMXV40T2Uklbo9Lf5asRjPzvZHmIfSIIcFA8DOXPtk2qpbfqkkyAZjl7AqNcUYgpgXQazQGICQmjKQjdOf9FgBSTNJbNCKsxAUlxRh1S7tXvjcb3pvW-qjV0dxyG5pucCp6N7LtjVXRgne9Cvu1N3YTcRtN6-2wPwRDO-POGeUiE8ZhEl-oLy7lob6ovdq1XaNsf49uNN959XCqE7R-nX_OFvHq4205m65iTjHt4zKlGS7STGqRM5aDplqInKqaC1JjkUONWUolB2CFLqUshCjD11IXohQsz9IJose70rXeO6WrzpmGu58KQ3UQWAWB1VlgdRIYsKcj1g0i7C7Q2VgIwDHwh7eDs-GL_2_-AqPsgik</recordid><startdate>20160324</startdate><enddate>20160324</enddate><creator>Jacob, Nicholas T</creator><creator>Lockner, Jonathan W</creator><creator>Schlosburg, Joel E</creator><creator>Ellis, Beverly A</creator><creator>Eubanks, Lisa M</creator><creator>Janda, Kim D</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20160324</creationdate><title>Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development</title><author>Jacob, Nicholas T ; Lockner, Jonathan W ; Schlosburg, Joel E ; Ellis, Beverly A ; Eubanks, Lisa M ; Janda, Kim D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a414t-93451835cfb76670f4fbb74edab2d1b70d1634ca0068f9cc8bb9480cf8b9b6753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antibody Formation - drug effects</topic><topic>Drug Carriers</topic><topic>Flagellin - chemistry</topic><topic>Haptens</topic><topic>Hypothermia - chemically induced</topic><topic>Hypothermia - prevention & control</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nicotine - analogs & derivatives</topic><topic>Nicotine - chemistry</topic><topic>Nicotine - immunology</topic><topic>Pain Measurement - drug effects</topic><topic>Serum Albumin, Bovine - chemistry</topic><topic>Serum Albumin, Bovine - immunology</topic><topic>Smoking Cessation</topic><topic>Structure-Activity Relationship</topic><topic>Vaccines - chemical synthesis</topic><topic>Vaccines - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jacob, Nicholas T</creatorcontrib><creatorcontrib>Lockner, Jonathan W</creatorcontrib><creatorcontrib>Schlosburg, Joel E</creatorcontrib><creatorcontrib>Ellis, Beverly A</creatorcontrib><creatorcontrib>Eubanks, Lisa M</creatorcontrib><creatorcontrib>Janda, Kim D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jacob, Nicholas T</au><au>Lockner, Jonathan W</au><au>Schlosburg, Joel E</au><au>Ellis, Beverly A</au><au>Eubanks, Lisa M</au><au>Janda, Kim D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2016-03-24</date><risdate>2016</risdate><volume>59</volume><issue>6</issue><spage>2523</spage><epage>2529</epage><pages>2523-2529</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>Despite efforts to produce suitable smoking cessation aids, addiction to nicotine continues to carry a substantive risk of recidivism. An attractive alternative to current therapies is the pharmacokinetic strategy of antinicotine vaccination. A major hurdle in the development of the strategy has been to elicit a sufficiently high antibody concentration to curb nicotine distribution to the brain. Herein, we detail investigations into a new hapten design, which was able to elicit an antibody response of significantly higher specificity for nicotine. We also explore the use of a mutant flagellin carrier protein with adjuvanting properties. 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| fulltext | fulltext |
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| ispartof | Journal of medicinal chemistry, 2016-03, Vol.59 (6), p.2523-2529 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Antibody Formation - drug effects Drug Carriers Flagellin - chemistry Haptens Hypothermia - chemically induced Hypothermia - prevention & control Male Mice Mice, Inbred BALB C Nicotine - analogs & derivatives Nicotine - chemistry Nicotine - immunology Pain Measurement - drug effects Serum Albumin, Bovine - chemistry Serum Albumin, Bovine - immunology Smoking Cessation Structure-Activity Relationship Vaccines - chemical synthesis Vaccines - pharmacology |
| title | Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development |
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