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

Megan Laudenbach, Federico Baruffaldi, Christine Robinson, Philipp Carter, Davis Seelig, Carly Baehr, Marco Pravetoni

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article number5508
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Interleukin-4
Opioid Analgesics
Vaccines
Oxycodone
Immunologic Factors
Diphtheria-Tetanus-Pertussis Vaccine
Cytokines
Peptides
Antibodies
Heroin
Brain
Lymphocyte Activation
Prescriptions
Proteins
B-Lymphocytes
Pharmacology
T-Lymphocytes
Serum
Pharmaceutical Preparations

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose. / Laudenbach, Megan; Baruffaldi, Federico; Robinson, Christine; Carter, Philipp; Seelig, Davis; Baehr, Carly; Pravetoni, Marco.

In: Scientific reports, Vol. 8, No. 1, 5508, 01.12.2018.

Research output: Contribution to journalArticle

Laudenbach, Megan ; Baruffaldi, Federico ; Robinson, Christine ; Carter, Philipp ; Seelig, Davis ; Baehr, Carly ; Pravetoni, Marco. / Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose. In: Scientific reports. 2018 ; Vol. 8, No. 1.
@article{0373dedef3994ffe80a30c9386948794,
title = "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.",
author = "Megan Laudenbach and Federico Baruffaldi and Christine Robinson and Philipp Carter and Davis Seelig and Carly Baehr and Marco Pravetoni",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-23777-6",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

AU - Laudenbach, Megan

AU - Baruffaldi, Federico

AU - Robinson, Christine

AU - Carter, Philipp

AU - Seelig, Davis

AU - Baehr, Carly

AU - Pravetoni, Marco

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85044942827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044942827&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-23777-6

DO - 10.1038/s41598-018-23777-6

M3 - Article

C2 - 29615715

AN - SCOPUS:85044942827

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 5508

ER -