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Principal Investigator: Fatima Alamin Awad Alkareem Hamid
Organization: UNIVERSITY OF MINNESOTA
Fiscal Year: 2024
Award: $31,294
Funding agency: National Institute on Drug Abuse
Project Abstract:
The highly complex OUD and overdose epidemic poses a huge public health and economic burden. Current
FDA-approved pharmacotherapies against OUD and overdose use opioid receptor agonists and antagonists.
These therapies show overall limited efficacy, due to their side effects, suboptimal patient access and
compliance, and liability for abuse and diversion. Vaccines offer a new treatment option that is both alternative
and complementary to existing measures. Preclinical testing demonstrated anti-opioids vaccines as a highly
selective long-lasting treatment and prophylactic strategy that protects against opioid-induced antinociception,
motor activity, respiratory depression, bradycardia, and self-administration in pre-clinical models. Previous
clinical trials of addiction vaccines showed proof of efficacy in those subjects who achieved the highest antibody
(Ab) titers, highlighting the need to design more effective vaccines and understanding the basis for variability in
individual efficacy. Hence, this proposal focuses on developing next-generation nanoparticle-based anti-opioid
vaccines and deciphering molecular and cellular mechanisms underlying their efficacy. Our team developed a
novel lipid polymer hybrid nanoparticles (LPNP) platform, that enhanced the efficacy of conjugate vaccines
against nicotine and oxycodone. Based on these preliminary data, we propose further dissecting the molecular
basis of this increased efficacy and testing how nanovaccines composition, and adjuvant display determine
innate and adaptive immune activation and whether specific cellular and molecular mechanisms underlie vaccine
efficacy against OUD. AIM1 will test the effect of different polymers and adjuvant display methods on efficacy of
nanovaccine against oxycodone. As well as how nanoformulation of conjugate vaccine affect the delivery and
bioavailability of vaccine components. Studies will investigate vaccine efficacy in mice, IgG antibody titer and Ig
subclass and vaccine kinetics in terms of biodistribution, accumulation and localization within spleen and lymph
nodes. AIM2 will elucidate whether different nanovaccine formulations show distinctions in innate and adaptive
immune responses. Studies will dissect innate immunity in vitro activation and in vivo dynamics in response to
vaccination, addressing key cell subsets contributing to efficacy, as well as assess the magnitude of B cell
responses. Results will provide a model vaccine that can be easily adapted to other abused substances. Such
information will guide future vaccine design and the rational selection of the most appropriate formulation for a
given antigen. The proposed mentored studies and this F31 fellowship are invaluable training and
professional development opportunity as I strive to become an independent scientist. This hypothesis-driven
multidisciplinary project encompasses various state-of-art approaches that are prerequisites to excel in
translational research at the interface of immunology, pharmacology and substance abuse. The mentorship of
NIDA-funded experts will ensure the successful completion of the proposed studies and the effective
communication of research findings to the scientific community.
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B-Lymphocyte><Mentors><Mentorship><Methods><Mice><Mice Mammals><Modeling><Molecular><Monitor><Motor Activity><Murine><Mus><Mφ><NIDA><Nanotechnology><National Institute of Drug Abuse><National Institute on Drug Abuse><Native Immunity><Natural Immunity><Nature><Nicotine><Non-Specific Immunity><Nonspecific Immunity><Opiate agonist><Opiate receptor agonist><Opiates><Opioid><Opioid agonist><Opioid receptor agonist><Overdose><Oxycodeinon><Oxycodone><Oxycodone SR><Oxycontin><Patients><Pharmaceutical Preparations><Pharmacology><Pharmacotherapy><Phase 1 Clinical Trials><Phase I Clinical Trials><Phentanyl><Physiologic Availability><Plasma><Plasma Cells><Plasma Serum><Plasmacytes><Polymers><Position><Positioning Attribute><Pre-Clinical Model><Preclinical Models><Preclinical Testing><Process><Public Health><Quantitative RTPCR><Quantitative Reverse Transcriptase PCR><Research><Respiratory Depression><Reticuloendothelial System, Serum, Plasma><Rewards><Roxicodone><SARS-CoV-2 vaccine><SARS-coronavirus-2 vaccine><Safety><Scientist><Self Administered><Self Administration><Serum><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 vaccine><Site><Spleen><Spleen Reticuloendothelial System><Structure of germinal center of lymph node><Substance Use Disorder><Substance abuse problem><T4 Cells><T4 Lymphocytes><TLR4><TLR4 gene><TLR7><TLR7 gene><Testing><Time><Toll Homologue><Toll-Like Receptor 7><Training><Translational Research><Translational Science><Translations><Vaccinated><Vaccination><Vaccine Design><Vaccines><Veiled Cells><Ventilatory Depression><abuse liability><abuse of substances><abuse potential><accessory cell><activated B cells><adaptive immune response><adaptive immunity><addiction><addictive disorder><antagonism><antagonist><antibody titering><antinociception><antinociceptive><career><coronavirus disease 2019 vaccine><coronavirus disease-19 vaccine><deliver vaccines><depressed breathing><depression of breathing><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><draining lymph node><drug treatment><drug/agent><evaluate vaccines><flow cytophotometry><fluorescence imaging><fluorescent imaging><glycolic acid><imaging in vivo><immune activation><immune modulators><immunogen><immunogenicity><improved><in vivo><in vivo evaluation><in vivo imaging><in vivo testing><individual heterogeneity><individual variability><individual variation><lipid based nanoparticle><lipid nanoparticle><lymph gland><lymph nodes><lymphnodes><migration><multidisciplinary><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nano formulation><nano particle><nano tech><nano technology><nano vaccine><nano-sized particle><nano-technological><nanocarrier><nanoformulation><nanoparticle><nanosized particle><nanotech><nanotechnological><nanovaccine><nanovessel><new approaches><new vaccines><next generation><next generation vaccines><nicotine vaccination><nicotine vaccine><novel><novel approaches><novel strategies><novel strategy><novel vaccines><opiate consumption><opiate drug use><opiate intake><opiate use><opiate use disorder><opioid consumption><opioid drug use><opioid intake><opioid use><opioid use disorder><overdose death><overdose fatalities><pharmacologic><phase I protocol><plasmocyte><poly(lactic acid)><polyclonal antibody><polylactic acid><polymer><polymeric><pre-clinical testing><prevent><preventing><prophylactic><public health emergency><qRTPCR><rational design><recruit><regional lymph node><resiquimod><response><secondary lymph organ><secondary lymphatic organ><secondary lymphoid organ><side effect><site targeted delivery><skills><substance abuse><substance use and disorder><success><targeted delivery><therapeutically effective><time use><toll-like receptor 4><trafficking><translation><translation research><translational investigation><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine candidate><vaccine candidates against SARS-CoV-2><vaccine delivery><vaccine development><vaccine efficacy><vaccine evaluation><vaccine for novel coronavirus><vaccine formulation><vaccine platform><vaccine screening><vaccine testing><vaccines preventing COVID><vaccines to prevent COVID><vaccinology>