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Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation
[Image: see text] Though cocaine abuse and addiction continue to have serious implications for health and society, no FDA-approved interventions have been developed. Anticocaine conjugate vaccines offer an attractive opportunity for addiction treatment; however, vaccines have thus far failed in clin...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949726/ https://www.ncbi.nlm.nih.gov/pubmed/29795751 http://dx.doi.org/10.1021/acsmedchemlett.8b00051 |
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author | Kimishima, Atsushi Olson, Margaret E. Natori, Yoshihiro Janda, Kim D. |
author_facet | Kimishima, Atsushi Olson, Margaret E. Natori, Yoshihiro Janda, Kim D. |
author_sort | Kimishima, Atsushi |
collection | PubMed |
description | [Image: see text] Though cocaine abuse and addiction continue to have serious implications for health and society, no FDA-approved interventions have been developed. Anticocaine conjugate vaccines offer an attractive opportunity for addiction treatment; however, vaccines have thus far failed in clinical trials. As a result, anticocaine vaccines must be further optimized to achieve clinical translation. Herein, we report a study on the relationship between vaccine efficacy and hapten stability toward hydrolysis. Two haptens developed by our laboratory, GND and GNE, were conjugated to tetanus toxoid (TT) and formulated with alum and cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) adjuvants, the optimal formulation in anticocaine vaccine design. GND, a diamide, is more hydrolytically stable than GNE, a monoamide, toward butyrylcholinesterases. Ultimately, both vaccines induced antibodies with high affinity for cocaine. In hyperlocomotion testing, GND-TT and GNE-TT vaccinated mice exhibited a robust blockade of cocaine’s stimulatory effects at all tested doses. Overall, antibodies raised against both haptens were highly effective in protecting mice from cocaine-induced psychostimulation. |
format | Online Article Text |
id | pubmed-5949726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-59497262018-05-23 Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation Kimishima, Atsushi Olson, Margaret E. Natori, Yoshihiro Janda, Kim D. ACS Med Chem Lett [Image: see text] Though cocaine abuse and addiction continue to have serious implications for health and society, no FDA-approved interventions have been developed. Anticocaine conjugate vaccines offer an attractive opportunity for addiction treatment; however, vaccines have thus far failed in clinical trials. As a result, anticocaine vaccines must be further optimized to achieve clinical translation. Herein, we report a study on the relationship between vaccine efficacy and hapten stability toward hydrolysis. Two haptens developed by our laboratory, GND and GNE, were conjugated to tetanus toxoid (TT) and formulated with alum and cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) adjuvants, the optimal formulation in anticocaine vaccine design. GND, a diamide, is more hydrolytically stable than GNE, a monoamide, toward butyrylcholinesterases. Ultimately, both vaccines induced antibodies with high affinity for cocaine. In hyperlocomotion testing, GND-TT and GNE-TT vaccinated mice exhibited a robust blockade of cocaine’s stimulatory effects at all tested doses. Overall, antibodies raised against both haptens were highly effective in protecting mice from cocaine-induced psychostimulation. American Chemical Society 2018-04-16 /pmc/articles/PMC5949726/ /pubmed/29795751 http://dx.doi.org/10.1021/acsmedchemlett.8b00051 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Kimishima, Atsushi Olson, Margaret E. Natori, Yoshihiro Janda, Kim D. Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation |
title | Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation |
title_full | Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation |
title_fullStr | Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation |
title_full_unstemmed | Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation |
title_short | Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation |
title_sort | efficient syntheses of cocaine vaccines and their in vivo evaluation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949726/ https://www.ncbi.nlm.nih.gov/pubmed/29795751 http://dx.doi.org/10.1021/acsmedchemlett.8b00051 |
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