2010
TLR9-Targeted Biodegradable Nanoparticles as Immunization Vectors Protect against West Nile Encephalitis
Demento SL, Bonafé N, Cui W, Kaech SM, Caplan MJ, Fikrig E, Ledizet M, Fahmy TM. TLR9-Targeted Biodegradable Nanoparticles as Immunization Vectors Protect against West Nile Encephalitis. The Journal Of Immunology 2010, 185: 2989-2997. PMID: 20660705, PMCID: PMC3753007, DOI: 10.4049/jimmunol.1000768.Peer-Reviewed Original ResearchConceptsBiodegradable nanoparticlesUnmodified nanoparticlesImmune responseNanoparticlesCell-mediated immune responsesRobust humoral responseTh1 immune responseEffector T cellsAg-specific lymphocytesTh2-biased responsesAdjuvant aluminum hydroxideWest Nile encephalitisVirus encephalitisWest Nile virusAgHumoral responseCpG oligodeoxynucleotideT cellsMouse modelLive virusInfectious agentsProtein AgVaccine developmentWN virusNile virus
2009
Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody
Sultana H, Foellmer HG, Neelakanta G, Oliphant T, Engle M, Ledizet M, Krishnan MN, Bonafé N, Anthony KG, Marasco WA, Kaplan P, Montgomery RR, Diamond MS, Koski RA, Fikrig E. Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody. The Journal Of Immunology 2009, 183: 650-660. PMID: 19535627, PMCID: PMC3690769, DOI: 10.4049/jimmunol.0900093.Peer-Reviewed Original ResearchConceptsWest Nile virus envelope proteinWest Nile virusVirus envelope proteinDengue virusCross-reactive human monoclonal antibodiesBlood-brain barrier permeabilityEnvelope proteinWest Nile virus infectionNeutralization escape variantsNile virusWest Nile encephalitisNeutralization escape mutantsHuman monoclonal antibodyFatal neurological diseaseParental West Nile virusFusion loopEscape variantsInflammatory responseBarrier permeabilityLethal encephalitisMAb11Virus infectionHuman mAbsEscape mutantsNeurological diseasesInflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy
Demento SL, Eisenbarth SC, Foellmer HG, Platt C, Caplan MJ, Saltzman W, Mellman I, Ledizet M, Fikrig E, Flavell RA, Fahmy TM. Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 2009, 27: 3013-3021. PMID: 19428913, PMCID: PMC2695996, DOI: 10.1016/j.vaccine.2009.03.034.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAnimalsAntibody FormationCarrier ProteinsCD8-Positive T-LymphocytesDendritic CellsLactic AcidLipopolysaccharidesMiceMice, Inbred C57BLNanoparticlesNLR Family, Pyrin Domain-Containing 3 ProteinPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerVaccinationViral Envelope ProteinsWest Nile FeverWest Nile Virus VaccinesConceptsPattern recognition receptorsToll-like receptorsInflammasome activationInnate immune system activationEffective adaptive immune responseIntracellular pattern recognition receptorsAntigen-presenting cellsAdaptive immune responsesWest Nile encephalitisImmune system activationInnate immune pathwaysWild-type macrophagesDendritic cellsCellular immunityVaccination approachesVaccine efficacyIL-1betaNLRP3 inflammasomeAdjuvant systemImmune responsePotent new approachMurine modelInflammasome activitySystem activationImmune pathwaysInflammasome-activating biodegradable nanoparticulates as vaccine delivery systems (135.80)
Fahmy T, DEMENTO S, Eisenbarth S, Caplan M, Saltzman W, Mellman I, Ledizet M, Fikrig E, Flavell R. Inflammasome-activating biodegradable nanoparticulates as vaccine delivery systems (135.80). The Journal Of Immunology 2009, 182: 135.80-135.80. DOI: 10.4049/jimmunol.182.supp.135.80.Peer-Reviewed Original ResearchToll-like receptorsIL-1βInflammasome activationProinflammatory cytokines IL-1βAntigen-presenting cellsClass of nanomaterialsCytokines IL-1βSurface of nanoparticlesWest Nile encephalitisInnate immune pathwaysVaccine delivery systemWild-type macrophagesCellular immunityVaccination approachesMurine modelInflammasome activityType macrophagesImmune pathwaysAdjuvant deliveryDanger signalsVaccine designModel antigenLipopolysaccharideAntigenBiocompatible polyesterToll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing
Town T, Bai F, Wang T, Kaplan AT, Qian F, Montgomery RR, Anderson JF, Flavell RA, Fikrig E. Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. Immunity 2009, 30: 242-253. PMID: 19200759, PMCID: PMC2707901, DOI: 10.1016/j.immuni.2008.11.012.Peer-Reviewed Original ResearchConceptsToll-like receptor 7West Nile virusReceptor 7WNV infectionImmune cell infiltrationLethal WNV infectionMyeloid differentiation factorIL-23 p19IL-23 responsesIL-12 p40West Nile encephalitisIL-12 p35Infected target cellsHost defense mechanismsRNA flavivirusInnate cytokinesWNV encephalitisInterleukin-12Cell infiltrationImmune cellsTarget organsVariable severityMiceTarget cellsTissue concentrations
2008
Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain
Wang P, Dai J, Bai F, Kong KF, Wong SJ, Montgomery RR, Madri JA, Fikrig E. Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain. Journal Of Virology 2008, 82: 8978-8985. PMID: 18632868, PMCID: PMC2546894, DOI: 10.1128/jvi.00314-08.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-9Blood-brain barrierWest Nile virusWNV entryMetalloproteinase-9MMP9 expressionWNV infectionIntact blood-brain barrierBlood-brain barrier permeabilityBrain viral loadWest Nile virus entryEvans blue leakageMosquito-borne encephalitisWest Nile encephalitisLethal WNV challengeWild-type miceCentral nervous systemType IV collagen degradationPeripheral viremiaViral loadLeukocyte infiltrateInflammatory cytokinesLikely multifactorialBarrier permeabilityHost cytokinesICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System
Dai J, Wang P, Bai F, Town T, Fikrig E. ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System. Journal Of Virology 2008, 82: 4164-4168. PMID: 18256150, PMCID: PMC2292986, DOI: 10.1128/jvi.02621-07.Peer-Reviewed Original ResearchConceptsWest Nile virusICAM-1Control animalsWest Nile virus neuroinvasionBlood-brain barrier leakagePathogenesis of encephalitisNile virusBlood-brain barrierLow viral loadWest Nile encephalitisCentral nervous systemICAM-1 participatesVirus neuroinvasionNeuronal damageLeukocyte infiltrationViral encephalitisViral loadBarrier leakageViral infectionNervous systemEncephalitisMiceICAMVirusAnimals
2006
Antiviral Peptides Targeting the West Nile Virus Envelope Protein
Bai F, Town T, Pradhan D, Cox J, Ashish, Ledizet M, Anderson JF, Flavell RA, Krueger JK, Koski RA, Fikrig E. Antiviral Peptides Targeting the West Nile Virus Envelope Protein. Journal Of Virology 2006, 81: 2047-2055. PMID: 17151121, PMCID: PMC1797586, DOI: 10.1128/jvi.01840-06.Peer-Reviewed Original ResearchConceptsWest Nile virusMurine blood-brain barrierEnvelope proteinBlood-brain barrierPeptide 9West Nile encephalitisWNV envelope proteinCentral nervous systemWest Nile virus envelope proteinCDNA phage display libraryBrain parenchymaVirus envelope proteinHuman encephalitisViral envelope proteinsWNV infectionControl animalsPeptide-1Nervous systemRelated flavivirusesDengue virusAntiviral activityNew therapeuticsInhibition concentrationAntiviral peptidesNile virus