Opioid-use disorder (OUD) and opioid-induced overdoses are widespread public health problems throughout the world. According to the 2016 National Survey on Drug Use and Health, 11.8 million people in the United States abused opioids the previous year (3). Since then, the death toll from opioid overdoses has only continued to rise. Medication-assisted therapy (MAT) is the dominant method used for treating substance use disorders. However, the success rate of MAT is low due to the inaccessibility of necessary medications, safety issues, and low compliance among patients (3). Now, researchers are exploring the possibility of a vaccine against opioids as an alternative method for treating and preventing opioid use disorder. Vaccines may provide a safer and more effective treatment method for preventing opioid abuse and overdose.
Vaccine candidates against opioids consist of three different structural components (2). The structurally-modified opioid molecules used in the vaccine do not elicit an immune response on their own (2). They need to be attached to a conjugate protein or macromolecular carrier (2). As the immunogenic component of the vaccine, the carrier protein or macromolecular carrier triggers an immune response in the body and, in the process, induces the body to produce antibodies against the opioid molecules. Finally, the opioid molecules and the conjugate protein or macromolecular carrier are attached to the adjuvant, which helps create a stronger immune response (2).
A viable vaccine that treats opioids safely must work by specifically preventing opioid molecules from crossing the blood-brain barrier, a semipermeable layer of endothelial cells that protects the brain from harmful substances (1). Opioid molecules are typically able to pass through this barrier and reach the brain easily due to their small size (1). When a patient is vaccinated against opioids, their body produces antibodies against opioid molecules. If they ingest opioids, these antibodies bind to the opioid molecules, making them too big to pass through the barrier (1). As a result, the drug molecules are unable to reach the brain and exert their psychological and physiological effects, preventing the patient from experiencing the pleasurable effects of opioids and protecting them from the risk of overdose (1). A key consideration is whether a vaccine also blocks the pain relieving effects of opioids, which are sometimes necessary in clinical contexts.
Although vaccines against substance abuse have demonstrated promising results in animal trials, they have shown limited efficacy in human subjects so far (4). In initial studies with nicotine and cocaine vaccines, only the top 30th percentile of subjects achieved a clinically significant level of antibodies that could protect them from the effects of these drugs (3). The high level of variance in the antibody response among human subjects suggests that individual factors play a big role in determining the effectiveness of vaccines against addictive substances (2). Researchers hypothesize that age, sex, the status of an individual’s immune system, and the amount and frequency of drug consumption could all affect the strength of the immune response elicited by anti-substance abuse vaccines (3).
In conclusion, vaccines are a promising avenue of research for developing a safer, longer-lasting, and more accessible way of treating opioid-use disorder compared to medication-assisted therapy. As candidates are tested in clinical trials, improving vaccine design and composition and taking into consideration individual factors that affect vaccine efficacy are important for developing a potent vaccine against opioids.
References
1. “A Shot Against Opioids.” National Institutes of Health HEAL Initiative, 10 Nov 2022, heal.nih.gov/news/stories/OUD-vaccine
2. Bloom, Benedict T, and Mary-Jessimine Bushell. “Vaccines against Drug Abuse-Are We There Yet?.” Vaccines vol. 10,6 860. 27 May. 2022, doi:10.3390/vaccines10060860
3. Pravetoni, Marco, and Sandra D Comer. “Development of vaccines to treat opioid use disorders and reduce incidence of overdose.” Neuropharmacology vol. 158 (2019): 107662. doi:10.1016/j.neuropharm.2019.06.001
4. Pugh, Laura. “Are Vaccines the Next Step in Controlling the Opioid Epidemic?” Johns Hopkins Medicine, 11 Apr 2019, biomedicalodyssey.blogs.hopkinsmedicine.org/2019/04/are-vaccines-the-next-step-in-controlling-the-opioid-epidemic/