Title page Combining a candidate vaccine for opioid use disorders with extended-release naltrexone increases protection against oxycodone-induced behavioral effects and toxicity. Michael D. Raleigha, Claudia Accetturob, and Marco Pravetonia,c,d*. aUniversity of Minnesota, School of Medicine, Department of Pharmacology, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis MN 55455, USA. bUniversita’ degli Studi di Milano, Socrates Program, 20 Via Giovanni Celoria, 18, 20133 Milano, Italy. cUniversity of Minnesota, School of Medicine, Department of Medicine, 420 Delaware Street SE, MMC 194 Suite 14-110 Phillips- Wangensteen Building Minneapolis, MN 55455, USA. dHennepin Healthcare Research Institute, 701 Park Avenue, Minneapolis, MN 55415, USA. Running Title Page Combination of opioid vaccine and naltrexone Corresponding author: Marco Pravetoni University of Minnesota Department of Pharmacology 3-108 Nils Hasselmo Hall 312 Church St SE, Minneapolis, MN 55455 612-625-6243,
[email protected] Number of text pages: 39 Number of tables: 0 Number of figures: 5 Number of references: 62 Number of words in the Abstract: 232 Number of words in the Introduction: 722 Number of words in the Discussion: 1498 Abbreviations: arterial oxygen saturation (SaO2), enzyme-linked immunosorbent assay (ELISA), extended release naltrexone (XR-NTX), good manufacturing practice (GMP), keyhole limpet hemocyanin (KLH), opioid use disorder (OUD), oxycodone (OXY), ovalbumin (OVA), percent maximum possible effect (%MPE) Recommended section assignment: Drug Discovery and Translational Medicine 2 Abstract Opioid use disorders (OUD) and opioid-related fatal overdoses are a significant public health concern in the United States and worldwide. To offer more effective medical interventions to treat or prevent OUD, anti-opioid vaccines are in development that reduce the distribution of the targeted opioids to brain and subsequently reduce the associated behavioral and toxic effects.