title: The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.
abstract: Translation of therapeutic vaccines for addiction, cancer, or other chronic noncommunicable diseases has been slow because only a small subset of immunized subjects achieved effective Ab levels. We hypothesize that individual variability in the number of naive and early-activated hapten-specific B cells determines postvaccination serum Ab levels and vaccine efficacy. Using a model vaccine against the highly abused prescription opioid oxycodone, the polyclonal B cell population specific for an oxycodone-based hapten (6OXY) was analyzed by flow cytometry paired with Ag-based magnetic enrichment. A higher frequency of 6OXY-specific B cells in either spleen biopsies or blood, before and after immunization, correlated to subsequent greater oxycodone-specific serum Ab titers and their efficacy in blocking oxycodone distribution to the brain and oxycodone-induced behavior in mice. The magnitude of 6OXY-specific B cell activation and vaccine efficacy was tightly correlated to the size of the CD4(+) T cell population. The frequency of enriched 6OXY-specific B cells was consistent across various mouse tissues. These data provide novel evidence that variations in the frequency of naive or early-activated vaccine-specific B and T cells can account for individual responses to vaccines and may predict the clinical efficacy of a therapeutic vaccine.
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN 55415;
authors.forename: Megan
authors.initials: M
authors.lastname: Laudenbach
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN 55415; Università degli Studi di Milano, Facoltà di Scienze del Farmaco, Milan, Italy 20133;
authors.forename: Federico
authors.initials: F
authors.lastname: Baruffaldi
authors.affiliation: Department of Chemistry, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Vervacke
authors.affiliation: Department of Chemistry, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Mark D
authors.initials: MD
authors.lastname: Distefano
authors.affiliation: Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Titcombe
authors.affiliation: Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mueller
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Tubo
authors.affiliation: Department of Urology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455; and.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Griffith
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN 55415; Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN 55455; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455 prave001@umn.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Pravetoni
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D004195:Disease Models, Animal; D018858:Germinal Center / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D010098:Oxycodone / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000906:Antibodies; D006241:Haptens; D014612:Vaccines; D010098:Oxycodone