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Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose.

ABSTRACT: Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation. Blockage of IL-4 signaling increased vaccine efficacy in blocking oxycodone distribution to the brain and protection against opioid-induced behavior and toxicity in mice. This strategy generalized to a peptide-protein conjugate immunogen, and a tetanus-diphtheria-pertussis vaccine. These data demonstrate that cytokine-based immunomodulators increase efficacy of vaccines against small molecules, peptides and proteins, and identify IL-4 as a pharmacological target for improving efficacy of next-generation vaccines.

SUBMITTER: Laudenbach M

PROVIDER: S-EPMC5882912 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose.

Laudenbach Megan M Baruffaldi Federico F Robinson Christine C Carter Philipp P Seelig Davis D Baehr Carly C Pravetoni Marco M

Scientific reports 20180403 1

Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators t ...[more]

PMID: 29615715

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Project description:BackgroundMedical settings provide ideal opportunities to identify patients with substance use disorders and provide harm reduction and treatment resources. Medical students often volunteer in the community and can spend substantial time with patients, serving as touchpoints. Accordingly, medical schools have begun training in harm reduction. Initial studies show such training acutely improves knowledge, but sustained effects remain unclear. This pilot study explored longer-term impacts of Opioid Overdose Prevention and Response Training (OOPRT) on medical student knowledge about opioids, overdose, and naloxone.MethodsStudents completed a survey about knowledge of opioid use disorder, overdoses, and attitudes towards patients. This included Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales. A subset of students was invited to attend OOPRT and complete a post-training survey. All who completed the baseline survey were invited to complete a 6-month follow-up. We analyzed long-term training effects on OOKS and OOAS scores.Results89 students completed baseline and 6-month follow-up surveys; of these, 22 received training. OOPRT yielded significant improvements in knowledge of signs of opioid overdose (F(2,38) = 18.04, P < .001), actions to take during overdose (F(2,38) = 8.32, P = .001), and naloxone use (F(2,38) = 35.46, P < .001), along with attitudes regarding overdose competencies (F(2,38) = 99.40, P < .001) and concerns (F(2,38) = 8.86, P < .001). When comparing over time, students who attended OOPRT retained significantly higher competency scores than those who did not attend F(1,87) = 40.82, P < .001). No other significant differences were observed.ConclusionsThis study demonstrates immediate efficacy of OOPRT in improving opioid overdose knowledge and attitudes and sustained changes at 6 months, compared to standard undergraduate medical curricula alone. Future research with larger sample sizes is underway to validate these preliminary findings and examine the difference in attitudes and knowledge retention over time. Given that students report interest in receiving OOPRT and consider it worthwhile, systematic study is warranted.

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Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose.

Publications

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose.

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