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 language | English (US) |
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Pages (from-to) | 74-86 |
Number of pages | 13 |
Journal | Journal of Immunological Methods |
Volume | 405 |
DOIs | |
State | Published - 2014 |
Bibliographical note
Funding Information:This work was supported by NIH NIDA DA034487 (Pravetoni M), a Minneapolis Medical Research Foundation Career Award (Pravetoni M) and the Irvington Fellowship Program of the Cancer Research Institute (Taylor JJ).
Keywords
- Addiction
- Antibodies
- B cell
- Prescription opioids
- Vaccine