Scientists receive NIH grant to develop an adjuvant vaccine for opioid use disorder

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Opioid addicts wage a daily war within over whether or not to use a drug whose side effect can be death. If those same addicts, however, had the choice to take an opioid vaccine once or twice a year, their internal struggle could be over.

With a $25 million grant from the National Institutes of Health Helping to End Addiction Long-term Initiative (HEAL), vaccine scientists from the Precision Vaccines Program at Boston Children's Hospital have partnered with Therese Kosten, University of Houston professor of psychology, and her colleagues Greg Cuny, associate professor of medicinal chemistry in the UH College of Pharmacy, and Dr. Colin Haile, MD, research assistant professor of psychology, to develop an adjuvant opioid use disorder vaccine.

An adjuvant molecule boosts the immune system's response to vaccines, a critical component for the effectiveness of anti-addiction vaccines.

The vaccine targets fentanyl, a synthetic and very potent opioid.

This could be a game changer for addiction."

Therese Kosten, Director, Developmental, Cognitive & Behavioral Neuroscience program, University of Houston

Kosten received $1.8 million of the grant to make the combination of the adjuvant with the vaccine as powerful as possible.

An anti-opioid vaccine would protect the brain and nervous system by stimulating the body to create powerful antibodies that target and bind to opioid molecules, preventing them from crossing the blood-brain barrier to reach the brain. By blocking opioids from the brain, the vaccine would reduce respiratory depression brought on by opioids when they reach the brain.

Fentanyl poses an especially difficult problem because it is often added to street drugs like cocaine, methamphetamines, and even counterfeit benzodiazepines like Xanax, which adds to the amount of fentanyl overdoses.

"Fentanyl is different than heroin or other opioids in the way that it stimulates the nervous system. It activates the same receptors in the brain as heroin or morphine but does so by a different mechanism, which makes drugs that can reverse a heroin overdose, like Narcan, almost ineffective against it," said Kosten.

Kosten's vaccine development follows work she and her spouse, Dr. Thomas Kosten, MD, who holds a joint appointment at UH and Baylor College of Medicine, previously developed and tested against cocaine.

"We will also evaluate multi-dose strategies, followed by single dose immunization, heterologous vaccination strategies, and the impact of waning immunity," said Kosten. The Kosten team will provide expert input into the regulatory strategy for meetings with the Food and Drug Administration based on their many years of experience in developing anti-addiction vaccines.

The number of opioid-related deaths has risen during the COVID-19 pandemic. According to the American Medical Association, more than 40 states are reporting increases in deaths from opioids. In June, a survey by the Centers for Disease Control and Prevention revealed that 13% of adult respondents in the U.S. reported starting or increasing opioid use to deal with stress or emotions related to the pandemic.

Leading the vaccine project in Boston are principal investigators Dr. Ofer Levy, MD, and David Dowling, of Boston Children's Precision Vaccines Program along with additional support from Dr. Sharon Levy, MD, director of Boston Children's Adolescent Substance Use and Addiction program and Elissa Weitzman of the Division of Adolescent and Young Adult Medicine.

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