Biologics to treat substance use disorders: Current status and new directions

Pravetoni, Marco

doi:10.1080/21645515.2016.1212785

Cited by 44 publications

(45 citation statements)

References 181 publications

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“…Vaccines and other biologics against substance use disorders have shown pre-clinical and clinical proof of concept, but no product has reached the market 5 – 10 . A major limitation to the translation of addiction vaccines is that clinical efficacy is observed only in the fraction of immunized subjects that display high levels of drug-specific antibodies 5 , 11 . This is a common shortcoming of vaccines consisting of purified protein subunits, or of proteins conjugated to peptides, carbohydrates, or synthetic small molecule haptens.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, the increased incidence in whooping cough is partially attributable to switching from the whole-cell pertussis vaccine to formulations containing the purified acellular pertussis subunit 12 . To increase efficacy, synthetic vaccines against substance use disorders are mixed with adjuvants or delivered via particle platforms 5 . However, a limited number of adjuvants or delivery systems are approved for human use because of potential side effects, and available adjuvants trigger innate immunity, but do not directly stimulate adaptive immunity 13 , 14 , suggesting that more effective immunization strategies are needed.…”

Section: Introductionmentioning

confidence: 99%

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Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Laudenbach

Baruffaldi

Robinson

et al. 2018

Sci Rep

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Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation. Blockage of IL-4 signaling increased vaccine efficacy in blocking oxycodone distribution to the brain and protection against opioid-induced behavior and toxicity in mice. This strategy generalized to a peptide-protein conjugate immunogen, and a tetanus-diphtheria-pertussis vaccine. These data demonstrate that cytokine-based immunomodulators increase efficacy of vaccines against small molecules, peptides and proteins, and identify IL-4 as a pharmacological target for improving efficacy of next-generation vaccines.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Laudenbach

Baruffaldi

Robinson

et al. 2018

Sci Rep

Self Cite

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“…Vaccines have been studied as potential adjuncts for the treatment of substance use disorders including nicotine [ 1 ], cocaine [ 2 ], methamphetamine [ 3 ] and opioids [ 4 ]. Key to their efficacy is their ability to elicit high concentrations of high affinity antibodies against those drugs [ 5 , 6 ]. Vaccines targeting opioids present some unique considerations with regard to their safety or efficacy.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse

et al. 2017

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Among vaccines aimed at treating substance use disorders, those targeting opioids present several unique medication development challenges. 1) Opioid overdose is a common complication of abuse, so it is desirable for an opioid vaccine to block the toxic as well as the addictive effects of opioids. 2) It is important that an opioid vaccine not interfere with the action of opioid antagonists used to reverse opioid overdose or treat addiction. 3) Some opioids are immunosuppressive and chronic ongoing opioid use could interfere with vaccine immunogenicity. 4) Although antibody-bound oxycodone is unable to enter the brain because of its size, it might still be able to activate peripheral opioid receptors. To assess vaccine impact on opioid toxicity, rats vaccinated with oxycodone conjugated to keyhole limpet hemocyanin subunit dimer (OXY-dKLH) adsorbed to alum or controls vaccinated with dKLH were compared with regard to oxycodone-induced hotplate analgesia and oxycodone-induced respiratory depression and bradycardia. Vaccination shifted the dose-response curves to the right, representing protection, for each of these endpoints. Naloxone was equally effective in both OXY-dKLH and control groups, providing complete and rapid reversal of respiratory depression. The administration of a long-acting naltrexone formulation during vaccination did not impair vaccine immunogenicity in mice. Similarly, serum anti-oxycodone antibody titers were not altered by continuous morphine infusion during vaccination compared to opioid-naïve controls. Competitive ELISA assay showed negligible or low affinity of immune antiserum for endogenous opioids or opioid antagonists. In vitro receptor binding assays showed that antibody-bound oxycodone does not activate mu opioid receptors. These data support further study of OXY-dKLH as a potential treatment for oxycodone abuse and suggest that vaccination might also reduce the severity of oxycodone overdose.

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“…Such vaccines have an advantage for long-term therapeutic use over pharmaceuticals targeting neural receptors by eliminating the medical complications and safety concerns of directly modulating neural signaling network. They also differ from other vaccines in that they are given to active users of drugs of abuse to prevent escalation of use or relapse and do not depend on herd immunity for effectiveness, so their efficacy is determined by individual responses to the vaccines (153).…”

Section: Vaccines With Non-traditional Antigensmentioning

confidence: 99%

Emerging Concepts and Technologies in Vaccine Development

et al. 2020

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Despite the success of vaccination to greatly mitigate or eliminate threat of diseases caused by pathogens, there are still known diseases and emerging pathogens for which the development of successful vaccines against them is inherently difficult. In addition, vaccine development for people with compromised immunity and other pre-existing medical conditions has remained a major challenge. Besides the traditional inactivated or live attenuated, virus-vectored and subunit vaccines, emerging non-viral vaccine technologies, such as viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer innovative approaches to address existing challenges of vaccine development. They have also significantly advanced our understanding of vaccine immunology and can guide future vaccine development for many diseases, including rapidly emerging infectious diseases, such as COVID-19, and diseases that have not traditionally been addressed by vaccination, such as cancers and substance abuse. This review provides an integrative discussion of new non-viral vaccine development technologies and their use to address the most fundamental and ongoing challenges of vaccine development.

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Biologics to treat substance use disorders: Current status and new directions

Cited by 44 publications

References 181 publications

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse

Emerging Concepts and Technologies in Vaccine Development

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