Current status and future prospects for the development of substance abuse vaccines

Heekin, R. David; Shorter, Daryl; Kosten, Thomas R.

doi:10.1080/14760584.2017.1378577

Cited by 37 publications

(28 citation statements)

References 78 publications

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“…Although approved medication assisted treatment (MAT) consisting of pharmacological agonists and antagonists of the opioid receptors is available, these medications display suboptimal clinical efficacy due to side effects, regulatory hurdles that limit patient access, and the potential for diversion and abuse [4][5][6][7][8] . As an alternative or complementary option to MAT, anti-opioid vaccines are an emerging strategy to counteract OUD and overdose [9][10][11] . Active immunization with opioid-based small molecule haptens conjugated to immunogenic carriers elicit production of drug-specific polyclonal antibodies, which selectively bind to the target drug in the blood and prevent its distribution to the brain [12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

et al. 2020

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Opioid use disorders (OUD) affect over 27 million people worldwide. Anti-opioid vaccines offer a promising strategy to treat OUD and prevent overdose. Using immunomodulation of cytokine signaling to increase vaccine efficacy, this study found that blocking IL-4 improved the efficacy of vaccines targeting oxycodone and fentanyl in male and female mice. Genetic deletion of the IL-4 receptor, STAT6, or antibody-based depletion of IL-13, did not increase vaccine efficacy against opioids, suggesting the involvement of type I IL-4 receptors. Enhancement of vaccine efficacy with blockade of IL-4 was associated with improved germinal center formation in secondary lymphoid organs and selective transcriptome signatures in the activated CD4+ T cell population subset. These data suggest that IL-4 is both a pharmacological target and a potential biomarker of vaccine efficacy against OUD.

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Section: Introductionmentioning

confidence: 99%

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

et al. 2020

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“…To date, two different vaccines for substance use disorder have been promoted to clinical trials. Vaccines for both nicotine and cocaine have failed to demonstrate effectiveness on primary endpoints in humans (for review, see [76,77]). Given these clinical trial failures, how should preclinical research proceed in evaluating immunopharmacotherapy effectiveness for OUD or other substance use disorders to enhance translatability of preclinical results to clinical testing?…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of Vaccines to Treat Opioid Use Disorders: How Close are We to a Clinically Viable Therapeutic?

Townsend¹,

Banks²

2020

CNS Drugs

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The ongoing opioid crisis, now into its second decade, represents a global public health challenge. Moreover, the opioid crisis has manifested despite clinical access to three approved opioid use disorder medications: the full opioid agonist methadone, the partial opioid agonist buprenorphine, and the opioid antagonist naltrexone. Although current opioid use disorder medications are underutilized, the ongoing opioid crisis has also identified the need for basic research to develop both safer and more effective opioid use disorder medications. Emerging preclinical evidence suggests that opioid-targeted vaccines or immunopharmacotherapies may be promising opioid use disorder therapeutics. One premise for this article is to critically examine whether vaccine effectiveness evaluated using preclinical antinociceptive endpoints is predictive of vaccine effectiveness on abuse-related endpoints such as drug self-administration, drug discrimination, and conditioned place preference. A second premise is to apply decades of knowledge in the preclinical evaluation of candidate small-molecule therapeutics for opioid use disorder to the preclinical evaluation of candidate opioid use disorder immunopharmacotherapies. We conclude with preclinical experimental design attributes to enhance preclinical-to-clinical translatability and potential future directions for immunopharmacotherapies to address the dynamic illicit opioid environment. Key Points Vaccine effectiveness should be assessed in terms of opioid agonist potency shifts. Vaccine effectiveness on a preclinical endpoint should be directly compared to effectiveness with naltrexone or buprenorphine treatment. Vaccine effectiveness should be evaluated on preclinical endpoints that are analogous to clinical opioid use disorder endpoints to enhance translational concordance.

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“…Dr. Thomas Kosten (University of Houston, Texas) summarized his more than two decades of work on anti-addiction vaccines ( 74 , 75 ). According to a 2018 substance use survey, ~165 million people aged ≥12 years in the USA (~60% of the population) were past month substance users ( e.g.…”

Section: Introductionmentioning

confidence: 99%

Towards Precision Vaccines: Lessons From the Second International Precision Vaccines Conference

et al. 2020

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Other than clean drinking water, vaccines have been the most effective public health intervention in human history, yet their full potential is still untapped. To date, vaccine development has been largely limited to empirical approaches focused on infectious diseases and has targeted entire populations, potentially disregarding distinct immunity in vulnerable populations such as infants, elders, and the immunocompromised. Over the past few decades innovations in genetic engineering, adjuvant discovery, formulation science, and systems biology have fueled rapid advances in vaccine research poised to consider demographic factors (e.g., age, sex, genetics, and epigenetics) in vaccine discovery and development. Current efforts are focused on leveraging novel approaches to vaccine discovery and development to optimize vaccinal antigen and, as needed, adjuvant systems to enhance vaccine immunogenicity while maintaining safety. These approaches are ushering in an era of precision vaccinology aimed at tailoring immunization for vulnerable populations with distinct immunity. To foster collaboration among leading vaccinologists, government, policy makers, industry partners, and funders from around the world, the Precision Vaccines Program at Boston Children's Hospital hosted the 2 nd International Precision Vaccines Conference (IPVC) at Harvard Medical School on the 17 th-18 th October 2019. The conference convened experts in vaccinology, including vaccine formulation and adjuvantation, immunology, cell signaling, systems biology, biostatistics, bioinformatics, as well as vaccines for non-infectious indications such as cancer and opioid use disorder. Herein we review highlights from the 2 nd IPVC and discuss key concepts in the field of precision vaccines.

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Current status and future prospects for the development of substance abuse vaccines

Cited by 37 publications

References 78 publications

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

Preclinical Evaluation of Vaccines to Treat Opioid Use Disorders: How Close are We to a Clinically Viable Therapeutic?

Towards Precision Vaccines: Lessons From the Second International Precision Vaccines Conference

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