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J Immunol Methods. 2014 Mar;405:74-86. doi: 10.1016/j.jim.2014.01.010. Epub 2014 Jan 23.

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

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University of Minnesota, Department of Microbiology, Center for Immunology, 2101 6th Street SE, 2-142 MBB, Minneapolis, MN 55455, USA.
Minneapolis Medical Research Foundation, 701 Park Avenue, Minneapolis, MN 55404, USA.
Minneapolis Medical Research Foundation, 701 Park Avenue, Minneapolis, MN 55404, USA; University of Minnesota, School of Medicine, Department of Medicine, 420 Delaware Street SE, MMC 194, Suite 14-110, Phillips-Wangensteen Building, Minneapolis, MN 55455, USA; University of Minnesota, School of Medicine, Department of Pharmacology, 6-120 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA. Electronic address:


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.


Addiction; Antibodies; B cell; Prescription opioids; Vaccine

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