Fentanyl vaccine prevents opioid overdose in rats

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2023-04-13

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Abstract

According to the latest figures from the AMA's Advocacy Resource Center, there has been a sharp increase in opioid related deaths in over 40 states. Opioid overdose is caused by severe respiratory depression that leads to heart failure and death. Research on potential treatments addressing the present emergence of Opioid Use Disorder (OUD) and opioid-associated death crisis in the United States is of extreme priority. Our lab is developing an anti-fentanyl (FEN) vaccine to prevent relapse and overdose. Here, we used a rodent model of overdose to test if our conjugate vaccine generates anti-fentanyl antibodies that block FEN from entering the brain and depressing heartrate, blood oxygen saturation and activity associated with FEN-induced overdose. Rats received FEN-CRM (5ug) conjugate with the adjuvant dmLT (1ug) at 0, 3 and 6 weeks. Serum samples were obtained at 6, 8 and 10 weeks and amounts of anti-FEN IgG antibodies were determined using ELISA. Rats were then administered FEN and physiological measures obtained over time. Vaccination with CRM-FEN produced appreciable amounts of anti-FEN antibodies that completely blocked FEN-induced decreases in heartrate, oxygen saturation and activity. Significant anti-FEN antibodies were produced that completely prevented fentanyl overdose in vaccinated but not in unvaccinated rats. These data support further development of this vaccine to address OUD and opioid-associated overdose deaths in humans. ***This project was completed with contributions from Elizabeth B. Norton from Tulane University.

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Mathematical biology

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