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Opioid-targeted vaccines represent an emerging treatment strategy for opioid use disorder. To determine whether concurrent vaccination against two commonly abused opioids (fentanyl and heroin) would confer broader spectrum opioid coverage, the current study evaluated dual fentanyl/heroin conjugate vaccine effectiveness using a warm water tail-withdrawal and a fentanyl/heroin-vs-food choice procedure in male and female rats across a 105-day observation period. Vaccine administration generated titers of high-affinity antibodies to both fentanyl and heroin sufficient to decrease the antinociceptive potency of fentanyl (25-fold), heroin (4.6-fold), and a 1:27 fentanyl/heroin mixture (7.5-fold). Vaccination did not alter the antinociceptive potency of the structurally dissimilar opioid agonist methadone. For comparison, continuous treatment with a naltrexone dose (0.032 mg/kg/h) shown previously to produce …