A) 6-hemisuccinyl morphine hapten used by Wainer et al. and linker extended hapten of Anton and Leff. B) Metabolic pathways of heroin (including isozyme abbreviations) and metabolite half lives in humans.

Vaccine titer levels over the course of 165 days. Vertical arrows represent booster injections at t = 14, 28, 53, 108 and 151 days. Data represented are the pooled sera mean value ± SEM.

Vaccination selectively blocks the thermal and mechanical antinociceptive effects of heroin. (A and B) Systemic injection of heroin (1 mg/kg, s.c.) produced robust decreases in both thermal (A) nociceptive sensitivity as measured by hot plate, and mechanical sensitivity (B) as measured by von Frey filament testing. This was fully reversed in the heroin-like vaccine (Her-11b) group. The morphine-like vaccine (Mor-12b) significantly blunted the thermal nociceptive effects of heroin compared to control, but was still significantly elevated from baseline and did not alter mechanical sensitivity. (C and D) Injection of the structurally similar opiate oxycodone produced similar thermal and mechanical insensitivity as seen with heroin. Neither the heroin-like (Her-11b) nor morphine-like (Mor-12b) vaccine altered antinociceptive responses to oxycodone. N = 7–8 per group, ***p < 0.001, 30 min post-drug versus baseline; ^#p < 0.05, ^###p < 0.001, versus KLH response post-drug.

(A and B) Acquisition of heroin self-administration is prevented in a subset of rats vaccinated with heroin-like immunoconjugate (Her-11b), but not morphine-like immunoconjugate (Mor-12b). The percentage of animals that obtain the acquisition criteria, maintaining at least 3 consecutive sessions of 3 infusions (60 μg/kg/infusion) or more, is significantly lower in a group of rats receiving heroin-like (Her-11b) vaccination compared to KLH controls (p < 0.05). Only 3 of 7 rats receiving Her-11b achieved criteria. Conversely, the morphine-like (Mor-12b) vaccine did not alter acquisition of heroin self-administration (p = 0.96). (C and D) Heroin- (Her-11b) and morphine-like (Mor-12b) vaccines do not alter the acquisition of self-administration of a natural reward. Animals were trained to press on an active for 0.1 ml of sweetened solution containing 0.125% w/v saccharine and 3% w/v glucose. When examining the percentage of animals that acquired the response criteria for the sweetened solution, defined as consecutive days of at least 30 or more responses, survival analysis revealed no significant differences based on vaccination treatment (Her-11b: p = 0.63, Mor-12b: p = 0.22 vs KLH control). N = 7–8 per group.

Synthesis of haptens 1–2 and conjugation to KLH carrier protein.