Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats

M. Pravetoni, M. D. Raleigh, M. Le Naour, A. M. Tucker, T. M. Harmon, J. M. Jones, A. K. Birnbaum, P. S. Portoghese, P. R. Pentel

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly) 4 linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components.

Original languageEnglish (US)
Pages (from-to)4617-4624
Number of pages8
JournalVaccine
Volume30
Issue number31
DOIs
StatePublished - Jun 29 2012

Fingerprint

Oxycodone
morphine
Morphine
Vaccines
narcotics
vaccines
Opioid Analgesics
brain
rats
Brain
glycyl-glycyl-glycyl-glycine
Antibodies
Immunization
antibodies
immunization
Heroin
6-O-monoacetylmorphine
Oxymorphone
Conjugate Vaccines
antigens

Keywords

  • Addiction
  • Antibodies
  • Heroin
  • Oxycodone
  • Prescription opioids
  • Vaccine

Cite this

Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats. / Pravetoni, M.; Raleigh, M. D.; Le Naour, M.; Tucker, A. M.; Harmon, T. M.; Jones, J. M.; Birnbaum, A. K.; Portoghese, P. S.; Pentel, P. R.

In: Vaccine, Vol. 30, No. 31, 29.06.2012, p. 4617-4624.

Research output: Contribution to journalArticle

Pravetoni, M. ; Raleigh, M. D. ; Le Naour, M. ; Tucker, A. M. ; Harmon, T. M. ; Jones, J. M. ; Birnbaum, A. K. ; Portoghese, P. S. ; Pentel, P. R. / Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats. In: Vaccine. 2012 ; Vol. 30, No. 31. pp. 4617-4624.
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