Scripps Research chemical biologists have developed a vaccine that blocks the effects of xylazine’s toxicity, a drug that has been illicitly added to opioids like fentanyl and heroin, leading to a rise in overdose deaths. The vaccine works by training the immune system to attack the drug, which was detailed in a new paper published in Chemical Communications on April 1, 2024. Xylazine intoxication presents similarly to opioid overdose, causing respiratory and central nervous system depression, and it can heighten the effects of opioids. Naloxone, typically administered to reverse the effects of opioids, does not counteract the impact of xylazine, underscoring the need for effective treatment options.
Researchers suspect that xylazine reduces blood flow to the brain and other parts of the body. The drug also causes non-healing skin lesions and wounds, usually on the forearms and lower legs, that can result in amputation in severe cases, earning it the nickname “zombie drug.” While no treatment currently exists, vaccines targeted at xylazine may offer a solution. Vaccines prompt the immune system to generate antibodies to combat invaders like viruses, bacteria, and toxins. However, some molecules are too small to trigger an immune response, such as xylazine, prompting researchers to create a vaccine using a design principle that pairs the drug molecule with a larger carrier molecule and an adjuvant.
In a study, researchers combined a xylazine hapten with various protein types to determine which combination would elicit a strong immune response against xylazine. Testing three vaccine formulations, the team observed that one of the vaccines significantly increased movement in mice given xylazine after 10 minutes, while two vaccines led to an improvement in breathing. Additionally, two of the three vaccines demonstrated a strong ability to prevent xylazine from reaching its receptors in the brain, limiting its adverse effects on the central nervous system.
A provisional patent has been filed on the research, and the team plans to further develop a bifunctional antibody that can reverse both fentanyl and xylazine’s toxicity simultaneously, a feat that naloxone cannot achieve. This strategy could have a significant impact on the opioid epidemic by providing both immediate and long-term protection from opioid substance use disorders and opioid-xylazine overdoses. “Evaluation of a Hapten Conjugate Vaccine Against the ‘Zombie Drug’ Xylazine” was co-authored by Mingliang Lin, Lisa M. Eubanks, Bin Zhou, and Kim D. Janda, with funding provided by the Shadek family and Pearson Foundation.
In conclusion, the development of a vaccine to counteract the effects of xylazine toxicity presents a promising avenue for treating acute toxicity resulting from xylazine exposure. This innovative approach leverages the immune system’s ability to generate antibodies against the drug, potentially providing a much-needed solution to the rising number of overdose deaths related to xylazine-laced opioids. Continued research into bifunctional antibodies that can combat both fentanyl and xylazine toxicity offers hope for a comprehensive treatment for substance use disorders and overdose incidents, with the potential to significantly impact the ongoing opioid epidemic.
