Synthetic opioids, primarily the class known as fentanyls, have surpassed prescription opioids as the most common drugs involved in overdose deaths in the United States, according to the Centers for Disease Control and Prevention.

Vaccine shows lasting effects against deadly synthetic opioids

May 02, 2019

LA JOLLA, CA – Scientists at Scripps Research have developed an experimental vaccine that may one day help treat addiction to fentanyl, a highly potent opioid linked to an epidemic of overdoses and fatalities in recent years.

In research published in the latest issue of the journal Neuropsychopharmacology, the team led by Kim Janda, PhD, showed that its vaccine produced months-long results in rats, decreasing dangerous drug-taking behavior and increasing behaviors maintained by healthier non-drug alternatives—in this case, choosing food over drugs.

Synthetic opioids, primarily the class known as fentanyls, have surpassed prescription opioids as the most common drugs involved in overdose deaths in the United States, according to the Centers for Disease Control and Prevention. By developing a novel vaccine against fentanyls, Janda and his team aim to diminish the “high” that results from taking this class of drug, thereby reducing rates of addiction and relapse.

This vaccine combines a fentanyl antigen with a modified tetanus toxin, since fentanyl on its own is unable to stimulate the production of antibodies. In this way, the vaccine cocktail elicits an immune response against the fentanyl family of synthetic opioids. Janda’s team recently took a similar approach in developing a vaccine candidate to address heroin addiction.

Once the vaccine was developed, researchers at Virginia Commonwealth University School of Medicine, led by Matthew Banks, PhD, investigated its effectiveness to decrease fentanyl self-administration and increase food self-administration in male and female rats.

“More effective and readily available treatments for opioid use disorder are needed to tackle the current crisis,” the study authors say. “One strategy includes using opioid-targeted vaccines to elicit antibody production by the host’s immune system that recognize and blunt the passage of fentanyl into the brain.”

The study relied on a behavioral procedure in which rats chose between receiving fentanyl injections or food. Before vaccine treatment, rats chose a large dose of fentanyl, but within four weeks of being vaccinated, fentanyl choices decreased, and food choices increased.

The effect was similar to that observed in rats chronically treated with naltrexone, an FDA-approved treatment for opioid addiction. In response to only two vaccinations at weeks one and three, fentanyl choice was decreased for 15 weeks, after which a third vaccination renewed the vaccine’s effect, suggesting a long-lasting vaccine response. Vaccination also prevented increased preference for fentanyl over food that is normally observed after fentanyl withdrawal.

“Vaccines provide many benefits over other forms of treatment for fentanyl addiction,” says Janda, who began investigating mechanisms for fentanyl vaccines many years before the current opioid crisis emerged, alarmed by its high potency and addictive potential. “Vaccines don’t require daily compliance with a medicine, are inexpensive to manufacture and can reduce the risk of overdose.”

Importantly, the fentanyl vaccine Janda’s team developed can block up to eight different clandestine fentanyl derivatives, including the drug known as “China White” and carfentanil—the most feared of the fentanyls, at some 10,000 times more lethal than morphine.

The findings suggest that immunotherapies that have the ability to sequester drugs, a class of drugs referred to as “immunopharmacotherapies,” may have the potential to prevent the development of opioid dependence and subsequent withdrawal. The research also suggests the vaccine may provide protection against unintended fentanyl overdose. Further evaluation of the present preclinical evidence in human laboratory studies and clinical trials is needed to confirm the effectiveness of the vaccine in human patients.

The authors caution that immunopharmacotherapies provide unique challenges compared with currently approved treatments. First, the vaccine relies on the individual’s ability to generate a sufficient immune response to the drug, which may be difficult in some individuals, such as those with weakened immune systems. Also, all vaccines, including the fentanyl vaccine used in this study, take several weeks to achieve maximal effectiveness. This lag time may leave subjects vulnerable to the effects of the targeted opioid during this vaccine induction period.

As a next step, Janda is looking to accelerate their synthetic opioid monoclonal antibody program, which is geared towards tackling carfentanil, which is in great need of effective treatments to prevent deadly overdoses. 

Additional authors of the study, “Conjugate vaccine produces long-lasting attenuation of fentanyl vs. food choice and blocks expression of opioid withdrawal-induced increases in fentanyl choice in rats,” include E. Andrew Townsend and Kaycee Faunce of the Virginia Commonwealth University School of Medicine; Steven Blake of Scripps Research; Candy S. Hwang of Scripps Research and Southern Connecticut State University; Yoshihiro Natori of Scripps Research and Tohoku Medical and Pharmaceutical University; and Bin Zhou and Paul T. Bremer of Scripps Research.   

This work was supported in part by grants from the National Institute of Mental Health International Study Group Investigating Drugs as Reinforcers travel award and the National Institute on Drug Abuse of the National Institutes of Health [UH3DA041146, T32DA007027, F32DA047026 and F32AI126628].

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