Scientists at the Scripps Research Institute (TSRI) in California have reported a major breakthrough in their efforts to develop a safe and effective vaccine to treat heroin addiction and and also prevent fatal overdoses. They have developed a new formulation that is safe in animal models and remains stable at room temperature for at least 30 days, making it almost ready for testing in humans.
“The heroin vaccine is one step closer to clinical evaluation,” said Candy S. Hwang, first author of the study and a research associate at TSRI.
The first formulation of the heroin vaccine was developed in 2013 by a team led byKim D. Janda, PhD, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI. It has been shown to be effective and safe in both mouse and non-human primate models.
The scientists say the new vaccine conditions immune system antibodies to recognize and bind to heroin molecules, blocking the drug from reaching the brain to cause a “high.” Blocking the high normally produced by taking heroin makes it much less likely that recovering addicts will relapse, according to the researchers, whose research was published in the journal Molecular Pharmaceutics.
Because the heroin molecule does not naturally prompt an antibody response, researchers attached it to a carrier protein that prompts the immune system to start making antibodies. The team also added an adjuvant to the vaccine, which heightens the immune response and makes the vaccine more effective.
“Our goal was to prepare a vaccine that could be advanced to clinical trials,” Hwang said. “As such, we were looking for the best combination of ‘hapten’ (the heroin molecule), carrier protein and adjuvant to keep the vaccine both stable for transport and storage, but still efficacious.”
To improve the vaccine, the scientists systematically evaluated 20 vaccine formulations with varying combinations of carrier proteins and adjuvants.
Their experiments in rodent models showed that the best vaccine formulation contained a carrier protein called tetanus toxoid (TT) and adjuvants called alum and CpG ODN. The discovery that alum worked best as an adjuvant was advantageous, the scientists said, since alum is one of the few adjuvants used in vaccines already approved by the U.S. Food and Drug Administration.
Their best vaccine formula provided protection even against normally lethal does of heroin, which is extremely important, considering the number of heroin addicts who have suffered fatal overdoses in relapsing while trying to quit using. “We believe that a heroin vaccine would be tremendously beneficial for people who have a heroin substance use disorder but have found difficulty in trying to quit,” Hwang said.
Hwang said more testing will be needed before human trials can begin. “We will need a vaccine that is stable and will last longer than a month,” he said.The other issue is being able to create large enough quantities to meet the demand. “With time, it looks promising,” said Hwang. “It would be such a benefit for people struggling with heroin substance use disorder.”
The researchers will also need to select a drug manufacturer to produce the vaccine on a large scale.
The research at Scripps dates back about 15 years, beginning with chemistry professor Dr. Kim Janda’s efforts to create a vaccine that can help the body combat heroin molecules in the same way vaccines help ward off a virus. The current study has been partially funded by the National Institutes of Health.