grant

Injectable Hydrogel Depots for Self-replicating mRNA Vaccine Delivery

Organization UNIVERSITY OF WASHINGTONLocation SEATTLE, UNITED STATESPosted 12 Jul 2022Deadline 30 Jun 2027
NIHUS FederalResearch GrantFY20253-D3-Dimensional3D7S Gamma GlobulinAIDS VirusAb responseAccountingAcquired Immune Deficiency Syndrome VirusAcquired Immunodeficiency Syndrome VirusAdjuvantAffinityAlginatesAntibiotic AgentsAntibiotic DrugsAntibioticsAntibodiesAntibody FormationAntibody ProductionAntibody titer measurementAntigensB blood cellsB cellB cellsB-CellsB-LymphocytesB-cellBacteremiaBacteriaBacterial AdhesinsBindingBiocompatible MaterialsBiomaterialsBolusBolus InfusionBone InfectionCOVID-19CV-19CathetersCause of DeathCell Communication and SignalingCell SignalingCell secretionCellular SecretionCessation of lifeChargeChitosanCoronavirus Infectious Disease 2019DNADataDeathDendritic CellsDeoxyribonucleic AcidDiagnosisDiseaseDisorderDoseExhibitsGelGenesGlycansHIVHospitalsHumanHuman Immunodeficiency VirusesHydrogelsIFN-GammaIFN-gIFN-γIFNGIFNγIgGImmune InterferonImmune responseImmunityImmunizationImmunizeImmunoglobulin GImplantIn VitroIndividualInfectionInfectious Skin DiseasesInjectableInjectionsInterferon GammaInterferon Type IIIntracellular Communication and SignalingIntravenousKineticsLAV-HTLV-IIILiquid substanceLung infectionsLymphadenopathy-Associated VirusM tuberculosis infectionM. tb infectionM. tuberculosis infectionM.tb infectionM.tuberculosis infectionMRSAMTB infectionMedical Care CostsMedical DeviceMembraneMemory B CellMemory B-LymphocyteMessenger RNAMethicillin ResistanceMethicillin Resistant S. AureusMiceMice MammalsMicrobial BiofilmsMiscellaneous AntibioticModelingModern ManMolecular InteractionMurineMusMycobacterium tuberculosis (MTB) infectionMycobacterium tuberculosis infectionNasalNasal Passages NoseNoseOsteomyelitisParticle SizePathogenicity FactorsPatientsPeptidesPersonsPhasePoliglusamPolymersPolysaccharidesPorosityProgram DevelopmentProsthesisProsthetic deviceProstheticsProtein SubunitsPublishingRNA vaccineRNA-based vaccineReactionReportingResistance to methicillinResistant to methicillinRespiratory System, Nose, Nasal PassagesS aureusS epidermidisS. aureusS. aureus infectionS. epidermidisSchiff BasesSepsisSeriesSignal TransductionSignal Transduction SystemsSignalingSiteSkin colonizationSplenocyteStaph aureusStaph aureus infectionStaphylococcus aureusStaphylococcus aureus infectionStaphylococcus epidermidisSubunit VaccinesSurvival RateSyringesSystemT cell responseT-CellsT-LymphocyteTB infectionTechnologyTextTransfectionTuberculosisUnited StatesVRSAVaccinesVancomycinVancomycin resistant S. aureusVancomycin resistant Staph aureusVancomycin-resistant S. aureusVancomycin-resistant S.aureusVancomycin-resistant Staphylococcus aureusVeiled CellsViral hepatitisVirulence FactorsVirus-HIVWorkadhesinantibody biosynthesisantibody titeringbacteraemiabacterial bloodstream infectionbacterial infection in the bloodstreambiofilmbiological materialbiological signal transductionblood infectionbloodstream infectioncopolymercoronavirus disease 2019coronavirus disease-19coronavirus infectious disease-19crosslinkcutaneous infectiondeliver vaccinesdesigndesigningdevelop a vaccinedevelop vaccinesdevelopment of a vaccinedisseminated TBdisseminated tuberculosisextracellularfluidhepatitis virus infectionhost responseimmune system responseimmunogenimmunoglobulin biosynthesisimmunoresponsein vivoinfected skininfected with S. aureusinfected with Staph aureusinfected with Staphylococcus aureusinfection due to Mycobacterium tuberculosisinfection in the bloodinfection of the bloodlFN-GammaliquidmRNAmRNA vaccinemRNA-based vaccinemedical costsmedical expensesmedical implantmembrane structuremethicillin resistance Staphylococcus aureusmethicillin resistantmethicillin resistant Staphylococcus aureusmethicillin resistant strains of Staphylococcus aureusnano meter scalenano meter sizednano particlenano-sized particlenanometer scalenanometer sizednanoparticlenanoscalenanosized particlenew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapyoutcome following vaccinationoutcome following vaccineplasmid vaccinepolymerpolymericporous hydrogelpre-clinical researchpreclinical researchpreventpreventingpulmonary infectionsresponseresult following vaccinationresult following vaccinescaffoldscaffoldingself assemblyskin infectionthree dimensionalthymus derived lymphocytetuberculosis infectiontuberculous spondyloarthropathyvaccination outcomevaccination resultvaccine deliveryvaccine developmentvaccine outcomevaccine resultvectorvector vaccine
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Full Description

While Staphylococcus aureus (SA) commonly asymptomatically colonizes the skin and nose of healthy
humans, severe disease can result from infection of the blood, bone, skin, and lungs, as well as sites of

catheters and prosthetic devices. With currently approved therapy, about one-third of patients diagnosed with

SA bacteremia succumb, accounting for more annual deaths than HIV, tuberculosis, and viral hepatitis

combined. This R01 will develop an injectable vaccine depot comprising: (a) previously published cationic

polymers to condense and charge neutralize anionic self-replicating mRNA (SR-mRNA) vaccines into

nanometer-sized particles (i.e., “polyplexes”) that are then incorporated within (b) our recently reported

injectable biodegradable gel of N-succinyl-chitosan (S-CS) and oxidized alginate (O-Alg). Ultimately, the

temporary CS-Alg depots completely biodegrade into non-toxic by-products that are eliminated. This project

will generate a self-immunizing biomaterials technology that is applied ONCE that is superior in immunization

versus repeated systemic bolus injections.

Grant Number: 5R01AI162840-04
NIH Institute/Center: NIH

Principal Investigator: James Bryers

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Injectable Hydrogel Depots for Self-replicating mRNA Vaccine Delivery — UNIVERSITY OF WASHINGTON | UNITED STATES | Jul 2 | Dev Procure