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Investigations into the efficacy of multi-component cocaine vaccines.

ABSTRACT: Although cocaine addiction remains a serious health and societal problem in the United States, no FDA-approved treatment has been developed. Vaccines offer an exciting strategy for the treatment of cocaine addiction; however, vaccine formulations need to be optimized to improve efficacy. Herein, we examine the effectiveness of a tricomponent cocaine vaccine, defined as having its hapten (GNE) and adjuvant (cytosine-guanine oligodeoxynucleotide 1826, CpG ODN 1826) covalently linked via the immunogenic protein ovalbumin (OVA). The tricomponent vaccine (GNE-OVA-CpG 1826) and a vaccine of analogous, individual components (GNE-OVA+CpG ODN 1826) were found to similarly induce highly specific anticocaine antibody production in mice and block cocaine's stimulant effects in hyperlocomotor testing.

SUBMITTER: Kimishima A

PROVIDER: S-EPMC6013332 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Investigations into the efficacy of multi-component cocaine vaccines.

Kimishima Atsushi A Olson Margaret E ME Janda Kim D KD

Bioorganic & medicinal chemistry letters 20171220 16

Although cocaine addiction remains a serious health and societal problem in the United States, no FDA-approved treatment has been developed. Vaccines offer an exciting strategy for the treatment of cocaine addiction; however, vaccine formulations need to be optimized to improve efficacy. Herein, we examine the effectiveness of a tricomponent cocaine vaccine, defined as having its hapten (GNE) and adjuvant (cytosine-guanine oligodeoxynucleotide 1826, CpG ODN 1826) covalently linked via the immuno ...[more]

PMID: 29317163

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Project description:ImportanceGenetic factors contribute to risk for bipolar disorder (BP), but its pathogenesis remains poorly understood. A focus on measuring multisystem quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that affect BP as well as its component phenotypes.ObjectiveTo identify quantitative neurocognitive, temperament-related, and neuroanatomical phenotypes that appear heritable and associated with severe BP (bipolar I disorder [BP-I]) and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk.Design, setting, and participantsMultigenerational pedigree study in 2 closely related, genetically isolated populations: the Central Valley of Costa Rica and Antioquia, Colombia. A total of 738 individuals, all from Central Valley of Costa Rica and Antioquia pedigrees, participated; among them, 181 have BP-I.Main outcomes and measuresFamilial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging, and diffusion tensor imaging phenotypes.ResultsOf 169 phenotypes investigated, 126 (75%) were significantly heritable and 53 (31%) were associated with BP-I. About one-quarter of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions as well as volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture.Conclusions and relevanceTo our knowledge, this is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I association within families that is consistent with expectations from case-control studies. Together, these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder.

Dataset Information

Investigations into the efficacy of multi-component cocaine vaccines.

Publications

Investigations into the efficacy of multi-component cocaine vaccines.

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