Dataset Information

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.

SUBMITTER: Laudenbach M

PROVIDER: S-EPMC4458396 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.

Laudenbach Megan M Baruffaldi Federico F Vervacke Jeffrey S JS Distefano Mark D MD Titcombe Philip J PJ Mueller Daniel L DL Tubo Noah J NJ Griffith Thomas S TS Pravetoni Marco M

Journal of immunology (Baltimore, Md. : 1950) 20150513 12

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 ox ...[more]

PMID: 25972483

Similar Datasets

Project description:ImportanceAlthough prescription opioids are the most common way adolescents and young adults initiate opioid use, many studies examine population-level risks following the first opioid prescription. There is currently a lack of understanding regarding how patterns of opioid prescribing following the first opioid exposure may be associated with long-term risks.ObjectiveTo identify distinct patterns of opioid prescribing following the first prescription using group-based trajectory modeling and examine the patient-, clinician-, and prescription-level factors that may be associated with trajectory membership during the first year.Design, setting, and participantsThis cohort study examined Pennsylvania Medicaid enrollees' claims data from 2010 through 2016. Participants were aged 10 to 21 years at time of first opioid prescription. Data analysis was performed in March 2020.Main outcomes and measuresThis study used group-based trajectory modeling and defined trajectory status by opioid fill.ResultsAmong the 189 477 youths who received an initial opioid prescription, 107 562 were female (56.8%), 81 915 were non-Latinx White (59.6%), and the median age was 16.9 (interquartile range [IQR], 14.6-18.8) years. During the subsequent year, 47 477 (25.1%) received at least one additional prescription. Among the models considered, the 2-group trajectory model had the best fit. Of those in the high-risk trajectory, 65.3% (n = 901) filled opioid prescriptions at month 12, in contrast to 13.1% (n = 6031) in the low-risk trajectory. Median age among the high-risk trajectory was 19.0 years (IQR, 17.1-20.0 years) compared with the low-risk trajectory (17.8 years [IQR, 15.8-19.4 years]). The high-risk trajectory received more potent prescriptions compared with the low-risk trajectory (median dosage of the index month for high-risk trajectory group: 10.0 MME/d [IQR, 5.0-21.2 MME/d] vs the low-risk trajectory group: 4.7 MME/d [IQR, 2.5-7.8 MME/d]; P < .001). The trajectories showed persistent differences with more youths in the high-risk trajectory going on to receive a diagnosis of opioid use disorder (30.0%; n = 412) compared with the low-risk group (10.1%; n = 4638) (P < .001).Conclusions and relevanceThis study's results identified 2 trajectories associated with elevated risk for persistent opioid receipt within 12 months following first opioid prescription. The high-risk trajectory was characterized by older age at time of first prescription, and longer and more potent first prescriptions. These findings suggest even short and low-dose opioid prescriptions can be associated with risks of persistent use for youths.

Project description:BackgroundThe unprecedented number of youths engaged in nonmedical use of prescription opioids (POs), as well as the myriad negative consequences of such misuse, emphasizes the importance of prevention efforts targeting this public health crisis. Although there are several science-based, interactive drug abuse prevention programs focused on preventing the use of nonprescription drugs in youths, to our knowledge, there are no science-based interactive programs that focus on the prevention of PO abuse among adolescents.ObjectiveThe aim of this study was to develop and conduct a formative evaluation of a science-based interactive Web-based program focused on the prevention of PO abuse among adolescents aged 12 to 17 years (Pop4Teens). This study was conducted to prepare for a randomized controlled trial designed to evaluate the effectiveness of Pop4Teens compared with an active control website, JustThinkTwice.com (Drug Enforcement Administration), in impacting knowledge and attitudes about POs and perceptions of risk associated with the abuse of POs, as well as intentions to use and actual use of POs.MethodsWe conducted 6 focus groups with 30 youths (a mean of 5 per group: the eligibility being aged 12-19 years) along a continuum of exposure to POs (in treatment for opioid use disorder, in general treatment for other substance use disorder, prescribed an opioid, and opioid-naïve) and writing sessions with 30 youths in treatment for opioid use disorder (12-19 years) to inform the development of the Web-based prevention tool. Feasibility and acceptability of a prototype of the Web-based intervention were then assessed through individual feedback sessions with 57 youths (drawn from the same populations as the focus groups).ResultsWe successfully completed the development of a Web-based PO abuse prevention program (Pop4Teens). Analyses of focus group transcripts informed the development of the program (eg, quiz content/format, script writing, and story editing). Selected writing session narratives anchored the planned scientific content by lending credibility and informing the development of compelling storylines intended to motivate the youth to engage with the program. Feedback session data indicated that the Web-based tool could be potentially useful and acceptable. In addition, feedback session participants demonstrated significant increases in their knowledge of key topics related to the prevention of PO abuse after the exposure to sections of the Web-based program.ConclusionsThe opioid crisis is predicted to get worse before it gets better. An effective response will likely require a multipronged strategy inclusive of effective evidence-based prevention programs acceptable to, and accessible by, a majority of youths.

Dataset Information

The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.

Publications

The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets