NOV 23, 2016 7:12 AM PST

TSRI Scientists Develop Vaccine Against Fatal Prescription Opioid Overdose


LA JOLLA, CA – November 23, 2016 – Scientists at The Scripps Research Institute (TSRI) have developed a vaccine that blocks the pain-numbing effects of the opioid drugs oxycodone (oxy) and hydrocodone (hydro) in animal models. The vaccine also appears to decrease the risk of fatal opioid overdose, a growing cause of death in the United States.

“We saw both blunting of the drug’s effects and, remarkably, prevention of drug lethality,” said Kim D. Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI. “The protection against overdose death was unforeseen but clearly of enormous potential clinical benefit.”

The study was published this week online ahead of print in the journal ACS Chemical Biology.
 

How It Works


The new oxy/hydro vaccine takes advantage of the immune system’s ability to recognize, seek out and neutralize invaders.

Opioids were designed to reach receptors in the brain, causing pain reduction and feelings of euphoria. For their vaccine, the researchers combined a signature opioid structure with a molecule to trigger an immune response. When injected, the vaccine teaches the immune system to bind to the drug molecule and remove it from circulation.

The vaccine-derived antibodies were tailored by TSRI scientists to seek out the prescription drug and block the opioid from reaching the brain, potentially depriving a person of the “reward” of consuming the drug, Janda explained.

The scientists believe a vaccine approach could have an advantage over current opioid addiction therapies because it would not alter brain chemistry like many of today’s anti-addiction therapies do.

“The vaccine approach stops the drug before it even gets to the brain,” said study co-author Cody J. Wenthur, a research associate in the Janda laboratory. “It’s like a preemptive strike.”
 

Lab Tests Show Promise


The researchers found that their vaccine design blocked pain perception of oxy/hydro use in mice. Indeed, those given the vaccine did not display the usual symptoms of a drug high, such as ignoring pain and discomfort.

In further tests, the rodents also appeared less susceptible to fatal overdose. Although it was found that some vaccinated mice did succumb to the opioid drug’s toxic effects, the researchers noted that it took much longer for the drug to impart its toxicity. If this effect holds true in humans, the vaccine could extend the window of time for clinical assistance if overdose occurs.

The scientists also discovered that the vaccine remained effective in mice for the entire 60-day study period, and they believe it has the potential to last even longer.

This oxy/hydro vaccine is not the first ever tested, but it is the first to use a faithful representation of the opioid in its design, which prompts the remarkable efficacy seen with the TSRI vaccine. “Our goal was to create a vaccine that mirrored the drug’s natural structure. Clearly this tactic provided a broadly useful opioid deterrent,” said study first author Atsushi Kimishima, a research associate in the Janda laboratory.

The study did raise some new questions. For example, researchers found that once antibodies bound to the drug, the drug stayed in the body—though neutralized—for a long time. The next steps will be to investigate this phenomenon and further study the optimal vaccine dose and injection schedule. The scientists also stated it may be possible to make the vaccine even more effective.

The additional author of the study, “An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life,” was Bin Zhou of TSRI.

This study was supported by the National Institute on Drug Abuse of the National Institutes of Health (grant 1UH2DA041146-02).

This article was originally published on Scripps.edu.
About the Author
  • The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists-including two Nobel laureates-work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
You May Also Like
MAR 04, 2021
Immunology
Why Do We Need Two Shots of the COVID Vaccine?
MAR 04, 2021
Why Do We Need Two Shots of the COVID Vaccine?
Unlike social distancing, mask-wearing, and hand hygiene, vaccines are our best bet as a long-term solution to protectin ...
MAY 06, 2021
Immunology
COVID Vaccines Don't Protect Everyone
MAY 06, 2021
COVID Vaccines Don't Protect Everyone
New research has revealed that COVID-19 vaccines may not work as effectively in those whose immune systems have been neg ...
MAY 19, 2021
Immunology
Intestinal Macrophages Promote Chronic Inflammation in Obesity
MAY 19, 2021
Intestinal Macrophages Promote Chronic Inflammation in Obesity
A research group from Switzerland hypothesized that immune cells in the gut (gastrointestinal tract) must trigger chroni ...
MAY 31, 2021
Immunology
Engineering Faster, More Agile T Cell Cancer Fighters
MAY 31, 2021
Engineering Faster, More Agile T Cell Cancer Fighters
Cell therapies use engineered T cells extracted from the patient’s own immune system to rally an attack on tumors. ...
JUN 07, 2021
Health & Medicine
Higher Incidence of Breast Cancer in Polluted Urban Areas
JUN 07, 2021
Higher Incidence of Breast Cancer in Polluted Urban Areas
A Taiwanese study looked at the incidence of breast cancer in areas of Taiwan with varying levels of air pollutants. Air ...
JUN 11, 2021
Cannabis Sciences
Does Cannabis Interact with the COVID Vaccine?
JUN 11, 2021
Does Cannabis Interact with the COVID Vaccine?
As of June 10th 2021, 43% of people in the US aged 12 and over have been fully vaccinated for COVID-19, with 5 ...
Loading Comments...