A treatment strategy for heroin addicts is to develop a vaccine against heroin that induces antibodies that bind heroin in the blood, preventing it from crossing the blood-brain barrier, and blocking the psychoactive effects of heroin. Heroin is too small of a molecule to induce antibodies and thus, a structural analog (hapten) must be coupled to a carrier protein to be used as a vaccine. The maximum number of haptens to attach to the carrier to induce the optimal antibody titer has not been reported. We coupled the heroin hapten (MorHap) to Tetanus toxoid (carrier) using maleimide-thiol coupling chemistry. The MorHap density of the Tetanus toxoid conjugates was measured using trinitrobenzenesulfonic acid (TNBS) assay, modified Ellman test and High Mass Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF). Analytical characterization of the conjugates showed that we were able to synthesize six Tetanus toxoid-MorHap conjugates with varying hapten densities.Tetanus toxoid-MorHap conjugates were mixed with liposomes containing Monophosphoryl Lipid A (PHAD�) to yield the heroin vaccine formulation. Female Balb/c mice were immunized 3 times at 3 week intervals with the heroin vaccine. Three weeks after the last immunization, vaccinated mice were challenged with heroin. Our data showed that mouse group immunized with Tetanus toxoid conjugate saturated with MorHap was best protected against the pain-relieving effects of heroin. Our results suggest that Tetanus-toxoid MorHap conjugates could abrogate the effects of heroin and thus, has a potential use to treat heroin addiction.

Development of a vaccine for the treatment of heroin addiction: Determination of the optimal heroin hapten-carrier density

248th National Meeting (2014)

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