Immunotherapy of 347 Volunteer Outpatient Morphine Addicts by Human Therapeutic Morphine Vaccine in Kermanshah Province of Iran

Akbarzadeh, Azim; Norouzian, D; Farhangi, Ali Akbar; Mehrabi, Mohammad Reza; Chiani, Mohsen; Zare, D.; Saffari, Zahra; Mortazavi, Mohammad Seddiq; Nikdel, A.

doi:10.3923/jpt.2009.30.35

Cited by 16 publications

(9 citation statements)

References 6 publications

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“…Opioid vaccines have been developed but none have been administered to humans, with the exception of a heroin vaccine studied in Iran but only sparingly described [ 32 , 33 ]. However vaccines for nicotine and cocaine have advanced to late stage clinical trails [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse

et al. 2017

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Among vaccines aimed at treating substance use disorders, those targeting opioids present several unique medication development challenges. 1) Opioid overdose is a common complication of abuse, so it is desirable for an opioid vaccine to block the toxic as well as the addictive effects of opioids. 2) It is important that an opioid vaccine not interfere with the action of opioid antagonists used to reverse opioid overdose or treat addiction. 3) Some opioids are immunosuppressive and chronic ongoing opioid use could interfere with vaccine immunogenicity. 4) Although antibody-bound oxycodone is unable to enter the brain because of its size, it might still be able to activate peripheral opioid receptors. To assess vaccine impact on opioid toxicity, rats vaccinated with oxycodone conjugated to keyhole limpet hemocyanin subunit dimer (OXY-dKLH) adsorbed to alum or controls vaccinated with dKLH were compared with regard to oxycodone-induced hotplate analgesia and oxycodone-induced respiratory depression and bradycardia. Vaccination shifted the dose-response curves to the right, representing protection, for each of these endpoints. Naloxone was equally effective in both OXY-dKLH and control groups, providing complete and rapid reversal of respiratory depression. The administration of a long-acting naltrexone formulation during vaccination did not impair vaccine immunogenicity in mice. Similarly, serum anti-oxycodone antibody titers were not altered by continuous morphine infusion during vaccination compared to opioid-naïve controls. Competitive ELISA assay showed negligible or low affinity of immune antiserum for endogenous opioids or opioid antagonists. In vitro receptor binding assays showed that antibody-bound oxycodone does not activate mu opioid receptors. These data support further study of OXY-dKLH as a potential treatment for oxycodone abuse and suggest that vaccination might also reduce the severity of oxycodone overdose.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse

et al. 2017

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“…They subsequently claimed that in Iran in 2002, 4.5% out of a population of 6,700,000 were morphine abusers. In 2009 and 2012, they reported successful results in vaccine trials with 347 and 436 morphine addicts [Akbarzadeh et al 2009;Farhangi et al 2012]. However, a BSA vaccine would not seem to be desirable for worldwide use, as antibodies against beef products would also be elicited.…”

Section: Morphine and Heroin Vaccinesmentioning

confidence: 99%

Vaccines against drugs of abuse: where are we now?

Kinsey

2014

Therapeutic Advances in Vaccines

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Drug addiction is a serious problem worldwide. One therapy being investigated is vaccines against drugs of abuse. The antibodies elicited against the drug can take up the drug and prevent it from reaching the reward centers in the brain. Few such vaccines have entered clinical trials, but research is going on apace. Many studies are very promising and more clinical trials should be coming out in the near future.

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“…Although several clinical trials of nicotine and cocaine vaccines have been conducted, 26–30 clinical evaluation of an opioid conjugate vaccine has been limited to a trial conducted in Iran, and for which scarce information is available. 31 One of the challenges in vaccine development is to use components and processes suitable for pharmaceutical manufacturing and regulatory approval. Continuous improvement of vaccine design, rational development of new vaccine components, and understanding the immunological mechanisms underlying effective immune responses against drugs of abuse will be important to speed translation of addiction vaccines.…”

Section: Introductionmentioning

confidence: 99%

“…Opioid vaccines are potentially safe and cost-effective immunotherapeutic interventions that elicit long-lasting opioid-specific antibodies, which decrease opioid distribution to the brain, reducing opioid self-administration, opioid-induced antinociception and locomotor activity, and opioid-induced respiratory depression and bradycardia, as well as fatal overdoses. − Preclinical proof of selectivity and efficacy has been shown against heroin and its metabolites, oxycodone, hydrocodone, and fentanyl in mouse, rat, and nonhuman primate studies. − ,− These data support translation of vaccines as a novel treatment strategy for OUD, and warrant their testing in clinical trials to demonstrate clinical proof of concept for this approach. Although several clinical trials of nicotine and cocaine vaccines have been conducted, − clinical evaluation of an opioid conjugate vaccine has been limited to a trial conducted in Iran, and for which scarce information is available . One of the challenges in vaccine development is to use components and processes suitable for pharmaceutical manufacturing and regulatory approval.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Efficacy and Characterization of Candidate Vaccines for Treatment of Opioid Use Disorders Using Clinically Viable Carrier Proteins

et al. 2018

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Vaccines may offer a new treatment strategy for opioid use disorders and opioid-related overdoses. To speed translation, this study evaluates opioid conjugate vaccines containing components suitable for pharmaceutical manufacturing and compares analytical assays for conjugate characterization. Three oxycodone-based haptens (OXY) containing either PEGylated or tetraglycine [(Gly)4] linkers were conjugated to a keyhole limpet hemocyanin (KLH) carrier protein via carbodiimide (EDAC) or maleimide chemistry. The EDAC-conjugated OXY(Gly)4-KLH was most effective in reducing oxycodone distribution to the brain in mice. Vaccine efficacy was T cell-dependent. The lead OXY hapten was conjugated to the KLH, tetanus toxoid, diphtheria cross-reactive material (CRM), as well as the E. coli-expressed CRM (EcoCRM) and nontoxic tetanus toxin heavy chain fragment C (rTTHc) carrier proteins. All vaccines induced early hapten-specific B cell expansion and showed equivalent efficacy against oxycodone in mice. However, some hapten-protein conjugates were easier to characterize for molecular weight and size. Finally, heroin vaccines formulated with either EcoCRM or KLH were equally effective in reducing heroin-induced antinociception and distribution to the brain of heroin and its metabolites in mice. This study identifies vaccine candidates and vaccine components for further development

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Immunotherapy of 347 Volunteer Outpatient Morphine Addicts by Human Therapeutic Morphine Vaccine in Kermanshah Province of Iran

Cited by 16 publications

References 6 publications

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse

Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse

Vaccines against drugs of abuse: where are we now?

Preclinical Efficacy and Characterization of Candidate Vaccines for Treatment of Opioid Use Disorders Using Clinically Viable Carrier Proteins

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