Hapten-specific naïve B cells are biomarkers of vaccine efficacy against drugs of abuse

J. J. Taylor, M. Laudenbach, A. M. Tucker, M. K. Jenkins, M. Pravetoni

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Vaccination against drugs of abuse shows efficacy in animal models, yet few subjects achieve effective serum antibody titers in clinical studies. A barrier to translation is the lack of pre-vaccination screening assays that predict the most effective conjugate vaccines or subjects amenable to vaccination. To address this obstacle, we developed a fluorescent antigen-based enrichment method paired with flow cytometry to characterize hapten-specific B cells. Using this approach, we studied naïve and activated B cells specific for structurally-related model haptens based on derivatization of the morphinan structure at the C6 position on oxycodone or at the C8 position on hydrocodone, and showing different pre-clinical efficacy against the prescription opioid oxycodone. Prior to vaccination, naïve B cells exhibited relatively higher affinity for the more effective C6-derivatized oxycodone-based hapten (6OXY) and the 6OXY-specific naïve B cell population contained a higher number of B cells with greater affinity for free oxycodone. Higher affinity of naïve B cells for hapten or oxycodone reflected greater efficacy of vaccination in blocking oxycodone distribution to brain in mice. Shortly after immunization, activated hapten-specific B cells were detected prior to oxycodone-specific serum antibodies and provided earlier evidence of vaccine failure or success. Analysis of hapten-specific naïve and activated B cells may aid rational vaccine design and provide screening tools to predict vaccine clinical efficacy against drugs of abuse or other small molecules.

Original languageEnglish (US)
Pages (from-to)74-86
Number of pages13
JournalJournal of Immunological Methods
Volume405
DOIs
StatePublished - 2014

Keywords

  • Addiction
  • Antibodies
  • B cell
  • Prescription opioids
  • Vaccine

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