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Vaccines in Development for Opioid Combinations

Heroin powder

Heroin powder (Drug Enforcement Administration)

22 August 2017. Researchers studying the immune system as a weapon against opioid addiction say they can develop vaccines that block combinations of opioids, like those sold on the street. A team from the lab of Scripps Research Institute chemistry professor Kim Janda discusses the status of these vaccines at this week’s national meeting of American Chemical Society in Washington, D.C.

The scale of the opioid abuse problem is huge. The ongoing problem of opioid addiction is intertwined with relief and management of pain, for which opioid drugs are usually prescribed. Opioids work by reducing the intensity of pain signals to the brain, particularly regions of the brain controlling emotion, which reduces effects of the pain stimulus. As of 2015, some 2 million Americans age 12 and older are addicted to prescription opioid drugs, while 600,000 are addicted to heroin. Drug overdose, mainly by opioids, is now the leading cause of death from unintentional injury in the U.S. Today, about 90 Americans die each day from opioid overdoses.

Like other opioids, fentanyl binds to receptors in the brain that control pain, but also emotions, and drives up dopamine levels in these brain regions. Fentanyl is a synthetic opioid, which given alone as an injection or patch is considered a powerful opioid pain killer — up to 500 times more powerful than morphine — but can become addictive. When mixed with street drugs, like heroin, the drug’s effects are amplified leading to sedation, unconsciousness, and coma, and sometimes death.

Janda and colleagues study the immune system as a better way of treating opioid addiction than most current therapies that aim at limiting the effects of addictive substances. For this purpose, the researchers are investigating therapeutic proteins combined with haptens, small molecules that give proteins the ability to induce an immune response. In the case of opioids, the vaccines aim to neutralize their chemical binding activity to opioid receptors, not just blunt their signals.

As reported in Science & Enterprise, the Scripps Institute team is already testing in lab animals a vaccine to counter the activity of fentanyl. And in a paper published in June 2017, the researchers reported on tests of a similar hapten-protein vaccine designed to block the potency of heroin. In both the cases, the vaccines produce high levels of antibodies in test animals, and sharply reduce the potency of the targeted fentanyl or heroin.

At this week’s meeting, Janda and colleagues discuss a key feature of the vaccines, namely their design to address specific opioid chemistries. This feature makes it possible to construct vaccines against specific combinations of opioids, such as fentanyl and heroin, often sold in illicit street transactions. The researchers say the heroin vaccine could also be combined with the maintenance drug methadone in a treatment program. In addition, results from the heroin tests suggest the vaccine could be designed as an overdose treatment.

The researchers describe as well extending the antibody strategy to other types of synthetic opioids and even non-opioid, but still addictive compounds.

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