grant

A Tunable Nanophage Platform for Vaccine Development

Organization UNIVERSITY OF COLORADO DENVERLocation Aurora, UNITED STATESPosted 20 Aug 2024Deadline 31 Jul 2026
NIHUS FederalResearch GrantFY20242019 novel corona virus2019 novel coronavirus2019-nCoV2019-nCoV variant2019-nCoV variant forms2019-nCoV variant strainsAddressAntibodiesAntibody ResponseAntigen PresentationAntigensArboviralArbovirusesAreaArthropod-Borne VirusesAvidityB blood cellsB cellB cellsB-CellsB-LymphocytesB-cellBacteriophagesBatsBiologicalBiological AgentBiological ProductsCHIKVCOVID crisisCOVID epidemicCOVID pandemicCOVID-19 crisisCOVID-19 epidemicCOVID-19 eraCOVID-19 global health crisisCOVID-19 global pandemicCOVID-19 health crisisCOVID-19 immunityCOVID-19 pandemicCOVID-19 periodCOVID-19 public health crisisCOVID-19 variantCOVID-19 variant formsCOVID-19 variant strainsCOVID-19 virusCOVID-19 yearsCOVID19 virusChikungunya virusChiropteraCoV-2CoV2Cold ChainsCoronaviridaeCoronavirusDataDevelopmentDiseaseDisorderDoseDrugsEBOVEbola virusEbola-like VirusesEngineeringFormulationFutureGenerationsGoalsHealthHumanitiesImmunizeImmunochemical ImmunologicImmunologicImmunologicalImmunologicallyImmunologicsInfectionInfluenza VirusIntramuscularLibrariesLigandsMERS corona virusMERS coronavirusMERS virusMERS-CoVMedicationMemoryMiceMice MammalsMiddle East Respiratory Syndrome Corona VirusMiddle East Respiratory Syndrome CoronavirusMiddle East Respiratory Syndrome VirusMiddle East Respiratory Syndrome-CoVMiddle East Respiratory VirusMiddle East Respiratory coronavirusMiddle Eastern Respiratory Syndrome Corona virusMiddle Eastern Respiratory Syndrome CoronavirusMiddle Eastern Respiratory Syndrome VirusMiddle Eastern Respiratory Syndrome-CoVMolecular ConfigurationMolecular ConformationMolecular StereochemistryMorbidityMorbidity - disease rateMurineMusOutcomeParamyxoviridaeParamyxovirusPathogenicityPathologicPhagesPharmaceutical PreparationsPolymersPolynucleotidesPreparationPropertyProteinsPublic HealthPublishingRNA vaccineRNA-based vaccineRapid screeningSARSSARS VirusSARS corona virusSARS corona virus 2SARS coronavirusSARS coronavirus diseaseSARS-Associated CoronavirusSARS-CO-V2SARS-COVID-2SARS-CoVSARS-CoV diseaseSARS-CoV-1SARS-CoV-2SARS-CoV-2 epidemicSARS-CoV-2 global health crisisSARS-CoV-2 global pandemicSARS-CoV-2 immunitySARS-CoV-2 pandemicSARS-CoV-2 variantSARS-CoV-2 variant formsSARS-CoV-2 variant strainsSARS-CoV2SARS-Related CoronavirusSARS-associated corona virus 2SARS-associated coronavirus 2SARS-coronavirus-2SARS-coronavirus-2 epidemicSARS-coronavirus-2 pandemicSARS-related corona virus 2SARS-related coronavirus 2SARSCoV2Severe Acute Respiratory CoronavirusSevere Acute Respiratory Coronavirus 2Severe Acute Respiratory Distress Syndrome CoV 2Severe Acute Respiratory Distress Syndrome Corona Virus 2Severe Acute Respiratory Distress Syndrome Coronavirus 2Severe Acute Respiratory SyndromeSevere Acute Respiratory Syndrome CoV 2Severe Acute Respiratory Syndrome CoV 2 epidemicSevere Acute Respiratory Syndrome CoV 2 pandemicSevere Acute Respiratory Syndrome CoV diseaseSevere Acute Respiratory Syndrome VirusSevere Acute Respiratory Syndrome corona virusSevere Acute Respiratory Syndrome coronavirusSevere Acute Respiratory Syndrome coronavirus diseaseSevere Acute Respiratory Syndrome-associated coronavirus 2Severe Acute Respiratory Syndrome-related coronavirus 2Severe acute respiratory syndrome associated corona virus 2Severe acute respiratory syndrome coronavirus 2Severe acute respiratory syndrome coronavirus 2 epidemicSevere acute respiratory syndrome coronavirus 2 immunitySevere acute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome related corona virus 2SurfaceSystemT cell responseTechnologyTestingVaccinesVariantVariationViralVirusWuhan coronavirusZIKVZika Virusatomic layer depositionbacterial virusbiologicbiologicsbiopharmaceuticalbiotherapeutic agentconformationconformationalconformational stateconformationallyconformationscorona viruscoronavirus disease 2019 crisiscoronavirus disease 2019 epidemiccoronavirus disease 2019 global health crisiscoronavirus disease 2019 global pandemiccoronavirus disease 2019 health crisiscoronavirus disease 2019 immunitycoronavirus disease 2019 pandemiccoronavirus disease 2019 public health crisiscoronavirus disease 2019 variantcoronavirus disease 2019 variant formscoronavirus disease 2019 variant strainscoronavirus disease 2019 viruscoronavirus disease crisiscoronavirus disease epidemiccoronavirus disease pandemiccoronavirus disease-19 global pandemiccoronavirus disease-19 pandemiccoronavirus disease-19 viruscoronavirus of pandemic concerncoronavirus of pandemic potentialcoronavirus vaccinecoronavirus with pandemic potentialdeploy vaccinesdesigndesigningdevelop a vaccinedevelop vaccinesdevelopment of a vaccinedevelopmentaldistribute vaccinesdrug/agentemerging pathogenevaluate vaccinesfull scale manufacturinghCoV19immunity against COVID-19immunity against SARS-CoV-2immunity against Severe acute respiratory syndrome coronavirus 2immunity against coronavirus disease 2019immunity to COVID-19immunity to SARS-CoV-2immunity to Severe acute respiratory syndrome coronavirus 2immunity to coronavirus disease 2019immunogenimmunogenicityinfluenzaviruslambda like Viruseslambda-Like Phageslarge scale manufacturinglarge scale productionmRNA vaccinemRNA-based vaccinemacromoleculemass productionmortalitymosaicnCoV2nano particlenano-sized particlenanoparticlenanosized particleneutralizing antibodynew pathogennovelnovel pathogenpandemic coronaviruspandemic threat coronavirusparticlepathogenpolymerpolymericpreparationsprotective efficacyreceptor bindingreceptor boundresponsescreeningscreeningssevere acute respiratory syndrome coronavirus 2 global health crisissevere acute respiratory syndrome coronavirus 2 global pandemicsevere acute respiratory syndrome coronavirus 2 variantsevere acute respiratory syndrome coronavirus 2 variant formssevere acute respiratory syndrome coronavirus 2 variant strainssevere acute respiratory syndrome-CoVstemthermolabilitythermostabilitytoolvaccine against coronavirusvaccine candidatevaccine candidate against coronavirusvaccine deploymentvaccine developmentvaccine distributionvaccine evaluationvaccine formulationvaccine platformvaccine roll-outvaccine rolloutvaccine screeningvaccine testingvirtualweapons of mass destructionzikav
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Full Description

PROJECT SUMMARY
Newly emerging and long-standing infectious challenges, including arboviruses, Ebola virus and pandemic
coronaviruses (CoVs), among others, pose serious public health concerns. Additionally, the potential use of
biological agents as weapons of mass destruction poses an ongoing threat to humanity. All of these issues
have in common the need for development strategies that allow for the rapid design, screening and
formulation of potential vaccine candidates. We have developed a “designer nanoparticle” platform based on
λ phage-like particles, or nanophages (NPs), that can display multiple antigenic biomolecules alone and in
combination in rigorously defined ratios. The NPs can be rapidly modified to screen and evaluate potential
vaccine candidates against newly emerging threats. Herein we propose to develop tools and technologies for
rapid screening of multivalent vaccine candidates effective for current and emerging SARS-CoVs and pre-
emergent SARS-like CoVs. We will engineer “second generation” nanophages (NPs) that display the spike
receptor binding domain (RBD) for these pathogens, the primary target of neutralizing antibody (Ab)
responses. Physiochemical and structural characterization of the preparations will be employed to ensure
that they possess properties that are appropriate for a pharmaceutical preparation. We will also employ a
novel atomic layer deposition technology to generate thermostable, timed-release, single-shot vaccine
formulations that reduce or eliminate onerous “cold-chain” requirements for their distribution. We further
propose to determine the immunogenicity and protective capacity of mosaic NPs engineered to
simultaneously display multiple antigens. These studies will identify vaccine candidates that elicit potent,
durable, and broad neutralizing Ab and T cell responses and protective immunity against SARS-CoV-2
variants and pre-emergent SARS-like bat CoVs. In addition to developing this powerful platform and
implementing novel formulation strategies, these studies will help define mechanisms of immunogenicity and
develop a platform for the rapid engineering of vaccine candidates for existing and untoward emerging
biological threats. In sum, this application seeks to provide compelling evidence that the  nanophage system
provides a platform for facile and rapid generation, and formulation of highly active multi-antigen presenting
vaccines.

Grant Number: 1R56AI186400-01
NIH Institute/Center: NIH
Principal Investigator: Carlos Catalano

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