Utility of fentanyl vaccines: unique challenges posed by preventing opioid overdose and treating opioid use disorder

Tunstall, Brendan J.; Vendruscolo, Leandro F.

doi:10.1038/s41386-019-0418-4

Cited by 8 publications

(6 citation statements)

References 7 publications

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“…Second, the specificity of the antibodies will also allow treatment of a vaccinated subject with structurally dissimilar opioids, such as oxycodone for pain management. However, Tunstall and Vendruscolo have succinctly posed two challenges regarding the utility of fentanyl vaccines in treating opioid use disorder 55 . First, a specific fentanyl vaccine may fail to target fentanyl analogs of a dissimilar chemical structure.…”

Section: Active Immunizationmentioning

confidence: 99%

Current status of immunotherapies for addiction

Kosten

2020

Annals of the New York Academy of Sciences

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The treatment of substance use disorders has always been challenging because multiple neurotransmitters mediate addiction. However, with smoking being the leading cause of preventable death and the recent opioid epidemic in the United States, the search for novel solutions becomes more imperative. In this review, we discuss the use of antibodies to treat addictions and highlight areas of success and areas that require improvement, using examples from cocaine, nicotine, and opioid vaccines. Through each example, we examine creative problem‐solving strategies for developing future vaccines, such as using an adenovirus vector as a carrier, designing bivalent vaccines, stimulating Toll‐like receptors for adjuvant effects, and altering the route of administration. Our review also covers passive immunization alone to override or prevent drug toxicity as well as in combination with vaccines for more rapid and potentially greater efficacy.

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Section: Active Immunizationmentioning

confidence: 99%

Current status of immunotherapies for addiction

Kosten

2020

Annals of the New York Academy of Sciences

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“… 19 Because vaccine-induced antibodies are highly specific for their target opioid, it is critical for vaccine research to stay ahead of structurally diverse fentanyl analogues. 20 In the present study, we explore the utility of fentanyl analogue-derived haptens in conjugate vaccines targeting fentanyl, alfentanil and acetylfentanyl. Alfentanil is a fast-acting fentanyl derivative used for anesthesia, 21 and acetylfentanyl (desmethyl fentanyl) is an impurity frequently encountered in illicit fentanyl and is less potent than fentanyl but with a narrow therapeutic window.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

et al. 2022

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The ongoing public health emergency of opioid use disorders (OUD) and overdose in the United States is largely driven by fentanyl and its related analogues and has resulted in over 75 673 deaths in 2021. Immunotherapeutics such as vaccines have been investigated as a potential interventional strategy complementary to current pharmacotherapies to reduce the incidence of OUD and opioid-related overdose. Given the importance of targeting structurally distinct fentanyl analogues, this study compared a previously established lead conjugate vaccine (F 1 –CRM) to a series of novel vaccines incorporating haptens derived from alfentanil and acetylfentanyl (F 8, 9a, 9b, 10 ), and evaluated their efficacy against drug-induced pharmacological effects in rats. While no vaccine tested provided significant protection against alfentanil, lead formulations were effective in reducing antinociception, respiratory depression, and bradycardia elicited by fentanyl, sufentanil, and acetylfentanyl. Compared with control, vaccination with F 1 –CRM also reduced drug levels in the brain of rats challenged with lethal doses of fentanyl. These data further support investigation of F 1 –CRM as a candidate vaccine against fentanyl and selected analogues.

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“…However, a heroin vaccine was ineffective in attenuating reinstatement induced by either heroin-associated audio/visual stimuli or a pharmacological stressor (e.g., yohimbine) [44]. Overall, these results provide evidence that immunopharmacotherapies primarily work on pharmacological mechanisms of drug relapse and may not be effective for drug-associated cue or stress-associated relapse conditions [58]. Moreover, the predictive validity of preclinical reinstatement procedures for candidate substance use disorder medication effectiveness has thus far been less robust compared to drug selfadministration procedures [59,60].…”

Section: Vaccine Effects On Relapse-related Endpoints Of Drug Self-admentioning

confidence: 84%

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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Utility of fentanyl vaccines: unique challenges posed by preventing opioid overdose and treating opioid use disorder

Cited by 8 publications

References 7 publications

Current status of immunotherapies for addiction

Current status of immunotherapies for addiction

Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

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

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