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Principal Investigator: Marco Pravetoni
Organization: VIRGINIA POLYTECHNIC INST AND ST UNIV
Fiscal Year: 2019
Award: $1,537,430
Funding agency: National Institute on Drug Abuse
Project Summary
Opioid use disorders (OUD) are a national public health emergency with more than 115 fatal overdoses occurring
each day in the USA. Annually, the economic burden of OUD is over US$78 billion. Several medications are
available for treating OUD, but their access is limited and efficacy is often sub-optimal. It is thus urgent to develop
new and affordable strategies to treat OUD. Immunopharmacotherapy has emerged as a promising treatment
approach against OUD. In contrast to traditional pharmacotherapies involving pharmacological agonists and
antagonists of the opioid receptors, immunopharmacotherapy relies on drug specific antibodies to bind the
circulating drug molecules to reduce their distribution to the brain, and thus reducing opioid-induced behaviors
and toxicity. Vaccination is likely the safer and more cost-effective immunopharmacotherapeutic intervention,
due to the ability of vaccines to trigger innate and adaptive immune responses in patients to offer long lasting
protection against OUD. Due to their selectivity, vaccines are not expected to interfere with endogenous opioids
nor with opioids used in pain management or treatment of OUD. Furthermore, it is possible to combine vaccines
with current medications for more effective OUD treatment because of the different mechanism of action. Current
anti-opioid vaccine candidates are primarily conjugate vaccines (opioid hapten-carrier protein conjugates)
delivered in adjuvants for immune recognition. Although these conjugate vaccines have shown promising pre-
clinical efficacy and selectivity against OUD, it is critical to test novel immunization platforms that may further
improve vaccine efficacy against OUD. Hence, the goal of this project is to fabricate novel nanoparticle-based
vaccines against OUD, which will likely lead to an effective immune response against the target opioid by offering
these unique features: 1) efficient presentation of B cell and T cell epitopes, 2) improved uptake of vaccine
particles by immune cells, and 3) incorporation of molecular adjuvants to promote a synergistic activation of
adaptive immune pathways. The innovation of this project involves merging Dr. Zhang's uniquely structured lipid-
polymer nanocarriers with Dr. Pravetoni's well-established opioid-based hapten series and pre-clinical platform
to identify vaccine candidates. Development will be staggered across UG3/UH3 phases, and we expect to
identify lead formulations of nanovaccines that offer protection against either oxycodone, fentanyl, or both at
once. The broad impact of this project resides in the rational design of nanoparticle-based vaccines that are safe
and effective against opioids. This novel nanoparticle-based immunization strategy can be applied to the
development of next-generation vaccines against a range of OUD and other substance use disorders.
Terms: <7S Gamma Globulin><Actiq><Adjuvant><Adverse effects><Agonist><Analytic Chemistry><Analytical Chemistry><Antibodies><Antibody Response><Antigen-Presenting Cells><Assay><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Behavior><Behavioral><Benchmarking><Best Practice Analysis><Binding><Bioassay><Biologic Assays><Biological Assay><Blood Serum><Brain><Brain Nervous System><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CRM-197><CRM197><Carrier Proteins><Cell Body><Cells><Charge><Combination Vaccines><Combined Vaccines><Common Rat Strains><Complex><Conjugate Vaccines><Corynebacterium Diphtheriae Toxin><Development><Dihydrohydroxycodeinone><Diphtheria Toxin><Dose><Drug Therapy><Drugs><Duragesic><Economic Burden><Encephalon><FDA approved><Fentanest><Fentanyl><Fentyl><Formulation><Future><Glycolates><Goals><Haptens><Hybrids><IgG><Immune><Immune response><Immunes><Immunization><Immunoactivators><Immunoadjuvants><Immunoglobulin G><Immunologic Adjuvants><Immunologic Sensitization><Immunologic Stimulation><Immunological Adjuvant><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunopotentiators><Immunostimulants><Immunostimulation><Incidence><Individual><Industry><Intervention><Intervention Strategies><Intravenous><KLH><KLH antigen><Keyhole Limpet Hemocyanin><Lead><Lipids><Maintenance><Medication><Mice><Mice Mammals><Modeling><Molecular><Molecular Interaction><Morphology><Murine><Mus><Nicotine><Opiate Antagonist><Opiate receptor antagonist><Opiates><Opioid><Opioid Antagonist><Opioid receptor antagonist><Overdose><Oxycodeinon><Oxycodone><Oxycodone SR><Oxycontin><Pain Control><Pain Therapy><Pain management><Pathway interactions><Patients><Pb element><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacology><Pharmacotherapy><Phase><Phentanyl><Polymers><Process><Production><Proteins><Rat><Rats Mammals><Rattus><Respiratory Depression><Roxicodone><Safety><Self Administration><Self-Administered><Series><Serum><Substance Use Disorder><Surface><T-Cell Epitopes><T-Lymphocyte Epitopes><T4 Cells><T4 Lymphocytes><Testing><Toxic effect><Toxicities><Toxicology><Transport Protein Gene><Transport Proteins><Transporter Protein><United States><Vaccinated><Vaccination><Vaccines><Ventilatory Depression><accessory cell><adaptive immune response><addiction><addictive disorder><base><chemical property><cost effective><cross reacting material 197><cross reactivity><depressed breathing><depression of breathing><design><designing><develop a vaccine><development of a vaccine><developmental><dosage><drug distribution><drug induced behavior><drug treatment><drug/agent><efficacy study><efficacy testing><endogenous opiate><endogenous opioids><experience><glycolic acid><heavy metal Pb><heavy metal lead><host response><immune adjuvant><immunogenicity><immunoresponse><improved><innovate><innovation><innovative><interventional strategy><keyhole-limpet hemacyanin><nano><nano carrier><nano formulation><nano particle><nano vaccine><nano-sized particle><nanocarrier><nanoformulation><nanoparticle><nanosized particle><nanovaccine><new approaches><new vaccines><next generation vaccines><non-medical opioid use><nonmedical opioid use><novel><novel approaches><novel strategies><novel strategy><novel vaccines><opiate consumption><opiate drug use><opiate intake><opiate misuse><opiate use><opiate use disorder><opioid consumption><opioid drug use><opioid intake><opioid misuse><opioid use><opioid use disorder><pain treatment><particle><pathway><physical property><pre-clinical><pre-clinical development><pre-clinical efficacy><preclinical><preclinical development><preclinical efficacy><public health emergency><response><safety study><safety testing><scale up><screening><small molecule><structured lipid><success><uptake><vaccine candidate><vaccine development><vaccine efficacy><vaccine formulation>