Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens

Abstract

Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (6OXY(Gly) 4 OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (6OXY(Gly) 4 -KLH) for the treatment of oxycodone abuse. In this study, oxycodonebased and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 6OXY(Gly) 4 -KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both

Dynamic vaccine blocks relapse to compulsive intake of heroin

“…This approach is becoming increasingly pertinent, with the increase in prescription opiate abuse raising concerns about vaccinated heroin addicts transitioning to alternative opiates. The design of vaccines against oxycodone and hydrocodone were also recently reported (39,40), along with examples of effective mixtures of multiple opiate vaccines (21,41), pointing to progress that will widen the spectrum of potential opiate blockade via vaccination.…”

Biologics to treat substance use disorders: Current status and new directions

“…75 The 6OXY(Gly) 4 -KLH was also more effective in blocking hydrocodone distribution to the brain and hydrocodone antinociception than immunogens containing C6-and C8-derivatized hydrocodone haptens. 75 Other positions on oxycodone and hydrocodone still remain to be explored. In contrast, development of heroin vaccines explored a wider range of hapten structures, generated from derivatization of the morphinan structure at the C3 and C6 position, [77][78][79][80][81][82] and at the bridgehead nitrogen 83,84 (reviewed in detail elsewhere 11,19 ).…”

“…[74][75][76] The 6OXY(Gly) 4 -KLH conjugate was more effective in blocking oxycodone distribution to the brain and oxycodone-induced antinociception than vaccines consisting of C6-oxycodone haptens conjugated to KLH through an hemisuccinate linker 74 or thiol-maleimide bondage. 75 The 6OXY(Gly) 4 -KLH was also more effective in blocking hydrocodone distribution to the brain and hydrocodone antinociception than immunogens containing C6-and C8-derivatized hydrocodone haptens. 75 Other positions on oxycodone and hydrocodone still remain to be explored.…”

“…75,[85][86][87] Increased efficacy of a heroin vaccine correlated with higher haptenization ratios in conjugates containing a tetanus toxoid (TT) carrier but not the diphtheria toxin crossreactive material (CRM 197 ) carrier. 88 Yet, haptenization ratio did not correlate with anti-heroin Ab titer nor affinity.…”

“…[90][91][92] To identify the most promising carrier suitable for translation of a vaccine against oxycodone and hydrocodone, BSA, decamer and dimer KLH, TT, and a TT-derived peptide were tested. 40,42,43,[74][75][76]93 To develop vaccines for treatment of methamphetamine abuse, for which no therapies exist, immunogens containing either native or dimer KLH, or TT, showed promising pre-clinical efficacy in blocking distribution of methamphetamine to the brain and blocking a variety of methamphetamine-induced behaviors, including intravenous self-administration. [94][95][96][97][98] Other carrier proteins have adjuvant-like properties, such as the well-characterized CRM 197 .…”