Using vaccines to harness the immune system and fight drugs of abuse

Shaffer, Leah

doi:10.1073/pnas.2121094118

Cited by 7 publications

(7 citation statements)

References 7 publications

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“…The hapten-acetamide tracer, 6-AmHap-acetamide (5), was also prepared following the common coupling procedure. Briefly, 2,5-dioxopyrrolidin-1-yl 3-((2-amino-2-oxoethyl)thio)propanoate (3; Scheme 1b) was synthesized from the reaction of commercially available 3-[(carbamoylmethyl)sulfanyl]propanoic acid with N-hydroxysuccinimide (NHS) in DMF.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Hapten-Fluorophore Synthesis. Sulfo-Cyanine5 Maleimide Conjugate of N- 3,4,4a,5,6,7,isoquinolin-9-yl)-3-mercaptopropanamide (2; 6-AmHap-Cy5). To a solution of trityl-protected thiol 1 (21 mg, 32 μmol) and triethylsilane (7.7 μL, 48 μmol) in dichloromethane (640 μL) was added trifluoroacetic acid (24.5 μL, 320 μmol) at 0 °C under an atmosphere of argon.…”

Section: Commerciallymentioning

confidence: 99%

“… 9 , 10 Hapten-based vaccines against opioids and other related drugs have been described in the literature. 3 , 5 , 6 , 11 − 14 …”

Section: Introductionmentioning

confidence: 99%

“…Therapeutic vaccines that induce drug-sequestering antibodies have been recognized as potential treatment modalities for opioid use disorder (OUD). − These antibodies negate the antinociceptive effects of the drugs by capturing and preventing them from permeating through the blood–brain barrier. , In order for this vaccine to effectively elicit an immune response, a hapten that structurally resembles the target drug is conjugated to an immunogenic carrier protein to allow the presentation of the hapten to the immune cells. , Hapten-based vaccines against opioids and other related drugs have been described in the literature. ,,,− …”

Section: Introductionmentioning

confidence: 99%

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A Rapid Method for Direct Quantification of Antibody Binding-Site Concentration in Serum

et al. 2022

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The quantitation of the available antibody binding-site concentration of polyclonal antibodies in serum is critical in defining the efficacy of vaccines against substances of abuse. We have conceptualized an equilibrium dialysis (ED)-based approach coupled with fluorimetry (ED-fluorimetry) to measure the antibody binding-site concentration to the ligand in an aqueous environment. The measured binding-site concentrations in monoclonal antibody (mAb) and sera samples from TT-6-AmHap-immunized rats by ED-fluorimetry are in agreement with those determined by a more established equilibrium dialysis coupled with ultraperformance liquid chromatography tandem mass spectrometry (ED-UPLC-MS/MS). Importantly, we have shown that the measured antibody binding-site concentrations to the ligand by ED-fluorimetry were not influenced by the sample serum matrix; thus, this method is valid for determining the binding-site concentration of polyclonal antibodies in sera samples. Further, we have demonstrated that under appropriate analytical conditions, this method resolved the total binding-site concentrations on a nanomolar scale with good accuracy and repeatability within the microliter sample volumes. This simple, rapid, and sample preparation-free approach has the potential to reliably perform quantitative antibody binding-site screening in serum and other more complex biological fluids.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Commerciallymentioning

confidence: 99%

“… 9 , 10 Hapten-based vaccines against opioids and other related drugs have been described in the literature. 3 , 5 , 6 , 11 − 14 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Rapid Method for Direct Quantification of Antibody Binding-Site Concentration in Serum

et al. 2022

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“…Abused drugs are small, non-immunogenic molecules that remain undetected by the immune system, allowing them to cross the blood-brain barrier to the reward centers within the brain [3,[5][6][7][8][9][10][11]. Current treatments for drug abuse include psychotherapy, pharmacotherapy, and combinations of both [1,12].…”

Section: Introductionmentioning

confidence: 99%

Vaccines against Drug Abuse—Are We There Yet?

Bloom

Bushell

2022

Vaccines

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Background: Drug abuse is a worldwide problem that is detrimental to public health. The potential for drug abuse extends to both legal and illicit drugs. Drawbacks associated with current treatments include limited effectiveness, potential side effects and, in some instances, the absence of or concerns with approved therapy options. A significant amount of clinical research has been conducted investigating immunotherapy as a treatment option against drug abuse. Vaccines against drug abuse have been the main area of research, and are the focus of this review. Methods: An extensive search using “EBSCOhost (Multiple database collection)” with all 28 databases enabled (including “Academic Search Ultimate”, “CINAHL Plus with Full Text”, and MEDLINE), interrogation of the ClinicalTrials.gov website, and searches of individual clinical trial registration numbers, was performed in February and March of 2022. This search extended to references within the obtained articles. Results: A total of 23 registered clinical trials for treating drug abuse were identified: 15 for treatment of nicotine abuse (all vaccine-based trials), 6 against cocaine abuse (4 were vaccine-based trials and 2 were metabolic-enzyme-based trials), 1 against methamphetamine abuse (a monoclonal-antibody-based trial), and 1 multivalent opioid treatment (vaccine-based trial). As indicated on the ClinicalTrials.gov website (Home—ClinicalTrials.gov), the status of all but two of these trials was “Completed”. Phase 3 clinical trials were completed only for vaccine treatments against nicotine abuse. Conclusion: Evidence in the form of efficacy data indicates that vaccines are not an option for treating nicotine or cocaine abuse. Efficacy data are yet to be obtained through completion of clinical trials for vaccines against opioid abuse. These findings align with the absence of regulatory approval for any of these treatments. This review further highlights the need for novel treatment strategies in instances where patients do not respond to current treatments, and while the search for efficacious vaccine-based treatments continues.

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