Drug overdose is currently the leading cause of accidental death in the U.S. 1 – in 2017 alone, over 47,000 Americans died from an opioid overdose, including from prescription opioids, heroin, and the powerful synthetic opioid fentanyl 2. The Centers for Disease Control and Prevention (CDC) estimate the annual economic burden of prescription opioid abuse in the U.S. to exceed $78 billion as a result of healthcare and addiction treatment costs, decreased work productivity, and criminal justice involvement 3. Further, the COVID-19 pandemic has dramatically overshadowed and exacerbated the opioid crisis; according to the CDC, 2020 was marked by 93,331 overdose deaths, reflecting the largest year-to-year increase (from 2019) in the last half-century. As an additional tool to fight opioid use disorder, a potential vaccine has gained prominent research attention. Initially proposed as early as the 1970s, the first in-human clinical trial assessing the potential of an opioid vaccine is currently underway.
One National Institutes of Health (NIH)-funded clinical research trial is currently seeking to assess whether potential opioid vaccines are safe, well-tolerated, and produce sufficient antibodies against opioids. The long-term vision following this first step would be to develop a multivalent vaccine against oxycodone, heroin, and other problematic opioids that blocks such substances from acting on the brain and causing addiction – a vaccine that also does not interfere with the use of opioid analgesia in medically appropriate situations 4.
The research will begin by assessing the safety of a trial vaccine (OXY-KLH) against the most commonly abused prescription opioid, oxycodone. Developed by a University of Minnesota professor 5, the vaccine is designed to prevent oxycodone from crossing the blood-brain barrier and penetrating the brain, where it acts to stimulate a euphoric high, may impair the brain’s centers controlling breathing, and can prove lethal in the case of an overdose. Preclinical studies had shown that this vaccine was safe and reduced rates of oxycodone self-administration among vaccinated animals. If the phase 1 trial demonstrates positive results, the vaccine would then need to be tested in phase 2 and phase 3 human clinical trials to assess its efficacy, which is likely to depend on the route of administration and opioid dose 6. Research will also seek to confirm whether the vaccine can prevent patients from feeling euphoric when administered oxycodone.
Thanks to its selectivity for oxycodone, the vaccine should not interfere with medications such as methadone, buprenorphine, naltrexone or naloxone; therefore, it has the potential to offer a long-lasting, safe and cost-effective complementary tool to standard opioid addiction treatments. In parallel, University of Minnesota researchers are monitoring the pharmacokinetic and immunological responses of trial participants in order to understand how the vaccine works, while also hoping to find clinically actionable biomarkers that may predict vaccine efficacy.
Future research plans to also assess the utility of a vaccine (M-KLH) against heroin/morphine. The ultimate vision is to develop a bivalent vaccine (OXY-KLH and M-KLH) targeting both oxycodone and heroin.
Given that six-month dropout rates for conventional opioid addiction treatments may reach up to 50%, vaccines are advantageous in that they are designed such that their effects last up to several months – an effective vaccine for opioid use disorder would protect at-risk individuals from an overdose while buying them time to re-enter a treatment program 7. A number of challenges remain to be addressed, however. First, the trial vaccine’s mechanisms remain to be fully elucidated. In addition, the trial vaccine is not expected to be effective in immunocompromised patients. Finally, key questions remain unanswered as regards insurance and payment 8. In the end, however, curbing the opioid epidemic requires a multipronged approach, and the development of a novel opioid use disorder vaccine would be a powerful and promising strategy.
References
1. Jones, G. H., Bruera, E., Abdi, S. & Kantarjian, H. M. The opioid epidemic in the United States—Overview, origins, and potential solutions. Cancer (2018). doi:10.1002/cncr.31713
2. NVSS – National Vital Statistics System Homepage. Available at: https://www.cdc.gov/nchs/nvss/index.htm.
3. Florence, C. S., Zhou, C., Luo, F. & Xu, L. The economic burden of prescription opioid overdose, abuse, and dependence in the United States, 2013. Med. Care (2016). doi:10.1097/MLR.0000000000000625
4. RePORT ⟩ RePORTER. Available at: https://reporter.nih.gov/search/QZ2UJymAfECtKu4892l6sw/project-details/9993692.
5. Marco Pravetoni, PhD | Medical School – University of Minnesota. Available at: https://med.umn.edu/bio/medical-discovery-teams/marco-pravetoni.
6. Raleigh, M. D. et al. Opioid dose-And route-dependent efficacy of oxycodone and heroin vaccines in rats. J. Pharmacol. Exp. Ther. (2018). doi:10.1124/jpet.117.247049
7. As Opioid Deaths Climb, Human Trials Begin for Vaccine. Available at: https://www.webmd.com/mental-health/addiction/news/20210915/opioid-vaccine-being-studied.
8. Government Accountability Office, U. GAO-19-706SP, Science & Tech Spotlight: Opioid Vaccines. doi:10.1016/j.tips.2018.08.001