Flu season is still going strong, meaning that almost every primary care visit concludes by ensuring that the patient has gotten their flu shot. There is no cure for the flu, but a simple shot greatly decreases an individual’s chances of contracting the virus and keeps epidemics from spreading in the population. What if we could address the opioid crisis with just such a simple method? According to a recent paper in Trends in Pharmacological Sciences, researchers at the Scripps Research Institute and Virginia Commonwealth University School of Medicine are investigating this question by training the immune system to produce antibodies against the deadliest opioids on the market today: fentanyl and carfentanil. With 130 Americans dying daily due to opioid overdoses, our country urgently needs new tools to combat the epidemic.
So how would such a vaccine work? In theory, individuals with Opioid Use Disorder (OUD) would be given a small dose of a particular opioid. The drugs alone do not produce any natural immune response, so they would be co-administered with another vaccine, such as the tetanus vaccine, that would naturally trigger the immune system to generate a response and produce antibodies against the opioid molecules themselves. When the individual then uses an opioid, those antibodies would “recognize” the opioid molecules in the blood and sequester them, preventing them from ever reaching their target receptors in the brain. Therefore, an individual could become “immune” to overdose — and would experience neither pain relief nor euphoria from the opioid.
Current overdose medications such as naloxone, available over the counter to all residents of Baltimore, target the receptors themselves and compete with the opioid, effectively “knocking it off” or causing the opioid to unbind from its receptor in the brain. This stops an overdose rapidly and effectively, but sends the patient immediately into withdrawal and thus does not decrease their desire for further opioids. Methadone, a widely used medication to treat opioid addiction, acts directly on the opioid receptors in the brain to decrease the associated euphoria and reduce the pain of withdrawal. An opioid vaccine, on the other hand, attempts to bypass the brain entirely and might help patients struggling with opioid use disorder by outright removing the physiologic response to opioids.
The hope for vaccines against drug use has emerged and gained significant traction in recent years. Researchers are evaluating vaccines not only for fentanyl and carfentanil, but also heroin, oxycodone, cocaine and nicotine. Vaccines have the potential to both prevent drug overdose deaths and remove the desire to take the drug at all. However, none have yet been approved by the FDA, although some anti-substance vaccines against other substances such as cocaine have made it to phase III clinical trials. So far, anti-substance use vaccines have been shown to be effective in animal models but not successfully translated to the complex human immune system, where responses can be unpredictable and difficult to consistently achieve across a large population. However, the Scripps team argues that its new opioid has better potential than anti-substance vaccines in the past. Past attempts have either failed to cause enough anti-drug antibody production, or produced antibodies that were not highly specific for the intended drug. This group claims they have addressed these issues by using tetanus toxin rather than other co-administered viral components to activate the immune system, and improving the quality of the opioid analog used in the vaccine to improve specificity for opioids.
In addition to biological challenges, the lack of proven effectiveness could relate to the complexities of addiction: patients may benefit from more traditional broad-based support and assistance in addition to a vaccine to address underlying drivers of substance use. Some patients and providers may also be concerned that a successful vaccine would prevent a vaccinated individual from feeling any pain relief from opioids after a serious procedure or other medically warranted use. However, a vaccine could someday be the boost someone needs to prevent overdose, reduce relapse and stay safe.
Banks, M. L., Olson, M. E., and Janda, K. D. (2018). “Immunopharmacotherapies for Treating Opioid Use Disorder.” Trends in Pharmacological Sciences, 39(11), 908-911. doi:10.1016/j.tips.2018.08.001
American College of Neuropsychopharmacology. "Vaccine could help address the opioid epidemic." ScienceDaily. ScienceDaily, 13 December 2018. www.sciencedaily.com/releases/2018/12/181213083650.htm
Bremer P.T. et al. “Development of a clinically viable heroin vaccine.” J. Am. Chem. Soc. 2017; 139: 8601-8611
Hackett, Don Ward. "Opioid Use Disorder Vaccines Nearing Finish Line." Precision Vaccinations. December 10, 2018. https://www.precisionvaccinations.com/opioid-vaccine-candidates-depend-exposure-opioid-molecules-produce-immune-response.
Martinez, Diana, and Trifilieff, Pierre. “Cocaine Vaccine: Research Review.” American Society of Addiction Medicine. October 14, 2014. https://www.asam.org/resources/publications/magazine/read/article/2014/10/15/cocaine-vaccine-research-review.
Volkow N.D. and Collins F.S. “The role of science in addressing the opioid crisis.” N. Engl. J. Med. 2017; 377: 391-394