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合成抗可卡因纳米疫苗成功预防可卡因诱导的过度活跃。

Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion.

机构信息

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.

Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.

出版信息

J Med Chem. 2023 Sep 14;66(17):12407-12419. doi: 10.1021/acs.jmedchem.3c00889. Epub 2023 Aug 30.


DOI:10.1021/acs.jmedchem.3c00889
PMID:37646732
Abstract

Cocaine is one of the most widely used and increasingly popular illicit psychoactive drugs. Unlike other commonly used substances of abuse, cocaine has no pharmacological therapies to treat addiction or aid in rehabilitation. Immunopharmacology has long been touted as a possible avenue to develop effective anticocaine therapies; however, lack of efficacy and designs which are not consistent with simple large-scale production have hindered vaccine translation. We have designed and synthesized a peptide-based anti-cocaine immunogen which we have shown is capable of inducing physiologically relevant immune responses in mice as part of a self-adjuvanting delivery system or in combination with the human-approved commercial adjuvant MF59. We have demonstrated that immunization with the reported vaccine elicits high titers of anti-cocaine IgG and prevents cocaine-induced hyperlocomotion in an in vivo murine model. This peptide-hapten immunogen along with self-adjuvanting liposomal-based delivery system provides a platform for the development of effective anti-drug vaccines.

摘要

可卡因是最广泛使用且日益流行的非法精神活性药物之一。与其他常用的滥用物质不同,可卡因没有药理学疗法来治疗成瘾或帮助康复。免疫药理学长期以来一直被吹捧为开发有效抗可卡因疗法的可能途径;然而,缺乏疗效以及不符合简单大规模生产的设计阻碍了疫苗的转化。我们设计并合成了一种基于肽的抗可卡因免疫原,我们已经证明它能够在作为自佐剂递送系统的一部分或与已批准的人类商业佐剂 MF59 联合使用的情况下,在小鼠中诱导具有生理相关性的免疫反应。我们已经证明,用报告的疫苗免疫可引起高滴度的抗可卡因 IgG,并防止体内小鼠模型中可卡因引起的过度活动。这种肽半抗原免疫原与基于自佐剂的脂质体递送系统一起为开发有效的抗药物疫苗提供了一个平台。

相似文献

[1]
Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion.

J Med Chem. 2023-9-14

[2]
Flagellin as carrier and adjuvant in cocaine vaccine development.

Mol Pharm. 2015-2-2

[3]
Adjuvants for vaccines to drugs of abuse and addiction.

Vaccine. 2014-8-8

[4]
Polyphosphazene: A New Adjuvant Platform for Cocaine Vaccine Development.

Mol Pharm. 2022-9-5

[5]
Efficient Syntheses of Cocaine Vaccines and Their Evaluation.

ACS Med Chem Lett. 2018-4-16

[6]
Hapten optimization for cocaine vaccine with improved cocaine recognition.

Chem Biol Drug Des. 2014-9

[7]
Efficacy, but not antibody titer or affinity, of a heroin hapten conjugate vaccine correlates with increasing hapten densities on tetanus toxoid, but not on CRM197 carriers.

Bioconjug Chem. 2015-6-17

[8]
Alum adjuvant is more effective than MF59 at prompting early germinal center formation in response to peptide-protein conjugates and enhancing efficacy of a vaccine against opioid use disorders.

Hum Vaccin Immunother. 2019-2-20

[9]
Suppression of Cocaine-Evoked Hyperactivity by Self-Adjuvanting and Multivalent Peptide Nanofiber Vaccines.

ACS Chem Neurosci. 2016-3-8

[10]
Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.

NPJ Vaccines. 2020-2-5

引用本文的文献

[1]
Automated Synthesis and Purification of Hydrophobic Peptides.

Methods Mol Biol. 2025

[2]
COT-TT vaccine attenuates induction and expression of cocaine-induced behavioral sensitization in rats: a dose-response study.

Front Psychiatry. 2025-6-3

[3]
A synthetic cyclic peptide for promoting antigen presentation and immune activation.

NPJ Vaccines. 2025-1-15

[4]
COT-TT vaccine attenuates cocaine-seeking and cocaine-conditioned place preference in rats.

Hum Vaccin Immunother. 2024-12-31

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