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Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice

Opioid use disorder (OUD) is a serious health problem that has dramatically increased over the last decade. Although current therapies for the management of OUD can be effective, they have limitations. The complementary strategy to combat the opioid crisis is the development of a conjugate vaccine t...

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Autores principales: Komla, Essie, Torres, Oscar B., Jalah, Rashmi, Sulima, Agnieszka, Beck, Zoltan, Alving, Carl R., Jacobson, Arthur E., Rice, Kenner C., Matyas, Gary R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229309/
https://www.ncbi.nlm.nih.gov/pubmed/34205869
http://dx.doi.org/10.3390/vaccines9060573
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author Komla, Essie
Torres, Oscar B.
Jalah, Rashmi
Sulima, Agnieszka
Beck, Zoltan
Alving, Carl R.
Jacobson, Arthur E.
Rice, Kenner C.
Matyas, Gary R.
author_facet Komla, Essie
Torres, Oscar B.
Jalah, Rashmi
Sulima, Agnieszka
Beck, Zoltan
Alving, Carl R.
Jacobson, Arthur E.
Rice, Kenner C.
Matyas, Gary R.
author_sort Komla, Essie
collection PubMed
description Opioid use disorder (OUD) is a serious health problem that has dramatically increased over the last decade. Although current therapies for the management of OUD can be effective, they have limitations. The complementary strategy to combat the opioid crisis is the development of a conjugate vaccine to generate high affinity antibodies in order to neutralize opioids in circulation before reaching the brain. The components of an opioid vaccine include an opioid hapten (6-AmHap) that is conjugated to a carrier protein (tetanus toxoid) with the addition of adjuvants (Army Liposome Formulation adsorbed to aluminum hydroxide-ALFA). There is no consensus in the literature as to whether preexisting immunity to the carrier protein may impact the immunogenicity of the conjugate vaccine by inducing an enhanced or suppressed immune response to the hapten. Here, we investigated whether pre-exposure to tetanus toxoid would affect the immunogenicity and efficacy of the heroin vaccine, TT-6-AmHap. Mice were primed with diphtheria, tetanus, and acellular pertussis (DTaP) vaccine at weeks -4 and -2, then immunized with TT-6-AmHap vaccine at weeks 0, 3, and 6. Using ELISA and behavioral assays, we found that preexisting immunity to tetanus toxoid had no influence on the immunogenicity and efficacy of the TT-6-AmHap vaccine.
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spelling pubmed-82293092021-06-26 Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice Komla, Essie Torres, Oscar B. Jalah, Rashmi Sulima, Agnieszka Beck, Zoltan Alving, Carl R. Jacobson, Arthur E. Rice, Kenner C. Matyas, Gary R. Vaccines (Basel) Article Opioid use disorder (OUD) is a serious health problem that has dramatically increased over the last decade. Although current therapies for the management of OUD can be effective, they have limitations. The complementary strategy to combat the opioid crisis is the development of a conjugate vaccine to generate high affinity antibodies in order to neutralize opioids in circulation before reaching the brain. The components of an opioid vaccine include an opioid hapten (6-AmHap) that is conjugated to a carrier protein (tetanus toxoid) with the addition of adjuvants (Army Liposome Formulation adsorbed to aluminum hydroxide-ALFA). There is no consensus in the literature as to whether preexisting immunity to the carrier protein may impact the immunogenicity of the conjugate vaccine by inducing an enhanced or suppressed immune response to the hapten. Here, we investigated whether pre-exposure to tetanus toxoid would affect the immunogenicity and efficacy of the heroin vaccine, TT-6-AmHap. Mice were primed with diphtheria, tetanus, and acellular pertussis (DTaP) vaccine at weeks -4 and -2, then immunized with TT-6-AmHap vaccine at weeks 0, 3, and 6. Using ELISA and behavioral assays, we found that preexisting immunity to tetanus toxoid had no influence on the immunogenicity and efficacy of the TT-6-AmHap vaccine. MDPI 2021-06-01 /pmc/articles/PMC8229309/ /pubmed/34205869 http://dx.doi.org/10.3390/vaccines9060573 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Komla, Essie
Torres, Oscar B.
Jalah, Rashmi
Sulima, Agnieszka
Beck, Zoltan
Alving, Carl R.
Jacobson, Arthur E.
Rice, Kenner C.
Matyas, Gary R.
Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice
title Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice
title_full Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice
title_fullStr Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice
title_full_unstemmed Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice
title_short Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice
title_sort effect of preexisting immunity to tetanus toxoid on the efficacy of tetanus toxoid-conjugated heroin vaccine in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229309/
https://www.ncbi.nlm.nih.gov/pubmed/34205869
http://dx.doi.org/10.3390/vaccines9060573
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