2022
The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice
Ullah I, Beaudoin-Bussières G, Symmes K, Cloutier M, Ducas E, Tauzin A, Laumaea A, Grunst M, Dionne K, Richard J, Bégin P, Mothes W, Kumar P, Bazin R, Finzi A, Uchil P. The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice. Cell Reports Medicine 2022, 4: 100893. PMID: 36584683, PMCID: PMC9799175, DOI: 10.1016/j.xcrm.2022.100893.Peer-Reviewed Original ResearchConceptsCOVID-19 convalescent plasmaFc effector functionsSARS-CoV-2 controlFc effector activityInnate immune cellsCCP efficacyHACE2 miceConvalescent plasmaImmunoglobulin levelsPlasma therapyImmune cellsTreatment efficacyDelays mortalityIgG fractionFc functionLow neutralizingTherapySecond lineMortalityMicePlasma contributesEfficacyFC activityProphylaxisIgGA Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection
Beaudoin-Bussières G, Chen Y, Ullah I, Prévost J, Tolbert WD, Symmes K, Ding S, Benlarbi M, Gong SY, Tauzin A, Gasser R, Chatterjee D, Vézina D, Goyette G, Richard J, Zhou F, Stamatatos L, McGuire AT, Charest H, Roger M, Pozharski E, Kumar P, Mothes W, Uchil PD, Pazgier M, Finzi A. A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection. Cell Reports 2022, 38: 110368. PMID: 35123652, PMCID: PMC8786652, DOI: 10.1016/j.celrep.2022.110368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingAntibodies, ViralAntibody-Dependent Cell CytotoxicityCOVID-19COVID-19 SerotherapyDisease Models, AnimalEpitopesHumansImmunization, PassiveImmunoglobulin Fab FragmentsImmunoglobulin Fc FragmentsMiceProtein BindingProtein ConformationSARS-CoV-2Spike Glycoprotein, Coronavirus
2021
Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy
Ullah I, Prévost J, Ladinsky MS, Stone H, Lu M, Anand SP, Beaudoin-Bussières G, Symmes K, Benlarbi M, Ding S, Gasser R, Fink C, Chen Y, Tauzin A, Goyette G, Bourassa C, Medjahed H, Mack M, Chung K, Wilen CB, Dekaban GA, Dikeakos JD, Bruce EA, Kaufmann DE, Stamatatos L, McGuire AT, Richard J, Pazgier M, Bjorkman PJ, Mothes W, Finzi A, Kumar P, Uchil PD. Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy. Immunity 2021, 54: 2143-2158.e15. PMID: 34453881, PMCID: PMC8372518, DOI: 10.1016/j.immuni.2021.08.015.Peer-Reviewed Original ResearchConceptsCOVID-19 convalescent subjectsSARS-CoV-2 infectionBioluminescence imagingK18-hACE2 miceLive bioluminescence imagingNatural killer cellsFc effector functionsSARS-CoV-2Convalescent subjectsKiller cellsPotent NAbsImmune protectionInflammatory responseEffector functionsNasal cavityNaB treatmentOptimal efficacyFc functionDepletion studiesMiceNAbsCOVID-19Direct neutralizationInfectionAntibodiesModulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir
Rajashekar JK, Richard J, Beloor J, Prévost J, Anand SP, Beaudoin-Bussières G, Shan L, Herndler-Brandstetter D, Gendron-Lepage G, Medjahed H, Bourassa C, Gaudette F, Ullah I, Symmes K, Peric A, Lindemuth E, Bibollet-Ruche F, Park J, Chen HC, Kaufmann DE, Hahn BH, Sodroski J, Pazgier M, Flavell RA, Smith AB, Finzi A, Kumar P. Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir. Cell Host & Microbe 2021, 29: 904-916.e6. PMID: 34019804, PMCID: PMC8214472, DOI: 10.1016/j.chom.2021.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingAntibody-Dependent Cell CytotoxicityAntiviral AgentsCD4 AntigensCD4-Positive T-LymphocytesCell LineEnv Gene Products, Human Immunodeficiency VirusEpitopesFemaleGlycoproteinsHEK293 CellsHIV InfectionsHIV-1HumansImmunoglobulin Fc FragmentsKiller Cells, NaturalMaleMiceMice, SCIDModels, AnimalProtein ConformationVirus ReplicationConceptsAntibody-dependent cellular cytotoxicityHIV-1 reservoirFc effector functionsViral reboundHumanized miceHIV-1HIV-1-infected individualsHIV-1-infected cellsAutologous HIV-1Natural killer cellsCD4-mimetic compoundsHIV-1 replicationSmall CD4-mimetic compoundsART interruptionFunctional cureNK cellsKiller cellsCellular cytotoxicityTherapeutic utilityInfected individualsCD4mcVirus reservoirMiceViral envelopeAntibody recognition
2019
Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice
Ventura JD, Beloor J, Allen E, Zhang T, Haugh KA, Uchil PD, Ochsenbauer C, Kieffer C, Kumar P, Hope TJ, Mothes W. Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice. PLOS Pathogens 2019, 15: e1008161. PMID: 31805155, PMCID: PMC6917343, DOI: 10.1371/journal.ppat.1008161.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHumanized miceCombination antiretroviral therapy regimenViral spreadHIV-1 infection dynamicsNon-invasive bioluminescentAntiretroviral therapy regimenHIV-1 reporterSame lymphoid tissuesInfected cell populationCART withdrawalInfection recrudescenceAntiretroviral therapyTreatment interruptionTherapy regimenLymphoid tissueInfection dynamicsART treatmentBioluminescent imagingInfectionViral infection dynamicsInfected cellsCell populationsMiceBioluminescent signalA Positioning Device for the Placement of Mice During Intranasal siRNA Delivery to the Central Nervous System.
Ullah I, Chung K, Beloor J, Lee SK, Kumar P. A Positioning Device for the Placement of Mice During Intranasal siRNA Delivery to the Central Nervous System. Journal Of Visualized Experiments 2019 PMID: 31475960, DOI: 10.3791/59201.Peer-Reviewed Original ResearchConceptsCentral nervous systemBlood-brain barrierNervous systemIntranasal drug deliveryBody temperatureMin rest periodMouse body temperatureCNS uptakeReceptor-binding domainRabies virus glycoproteinCNS deliveryAnesthetized miceDominant handNondominant handMiceInhalationDelivery of siRNASiRNA approachDelivery of drugsRest periodHeating padMouse headAdministrationVirus glycoproteinForward positionA Positioning Device for the Placement of Mice During Intranasal siRNA Delivery to the Central Nervous System
Ullah I, Chung K, Beloor J, Lee S, Kumar P. A Positioning Device for the Placement of Mice During Intranasal siRNA Delivery to the Central Nervous System. Journal Of Visualized Experiments 2019 DOI: 10.3791/59201-v.Peer-Reviewed Original Research
2015
Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice
Liu S, Jackson A, Beloor J, Kumar P, Sutton RE. Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice. Human Gene Therapy 2015, 26: 622-634. PMID: 25953321, PMCID: PMC4575530, DOI: 10.1089/hum.2014.146.Peer-Reviewed Original ResearchConceptsHumanized miceHuman immunodeficiency virus type 1 (HIV-1) acquisitionHuman immunodeficiency virus type 1Immunodeficiency virus type 1Plasma viral loadHigher serum levelsSingle intramuscular injectionBroadly Neutralizing AntibodiesVirus type 1First-generation adenoviral vectorsSerum levelsViral loadNeutralizing antibodiesIntramuscular injectionEffective vaccineT cellsHIV-1Therapeutic approachesHigh doseTherapeutic useType 1Adenoviral vectorAdV vectorsMiceAntibodies
2013
Site-specific Genome Editing in PBMCs With PLGA Nanoparticle-delivered PNAs Confers HIV-1 Resistance in Humanized Mice
Schleifman EB, McNeer NA, Jackson A, Yamtich J, Brehm MA, Shultz LD, Greiner DL, Kumar P, Saltzman WM, Glazer PM. Site-specific Genome Editing in PBMCs With PLGA Nanoparticle-delivered PNAs Confers HIV-1 Resistance in Humanized Mice. Molecular Therapy - Nucleic Acids 2013, 2: e135. PMID: 24253260, PMCID: PMC3889188, DOI: 10.1038/mtna.2013.59.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsHIV-1 resistanceHumanized miceCCR5 geneMolecular Therapy-Nucleic Acids (2013) 2Plasma viral RNA loadNOD-scid ILR5-tropic strainsBlood mononuclear cellsViral RNA loadWeeks posttransplantationControl miceMononuclear cellsRNA loadT cellsHIV-1Biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticlesCCR2 geneSingle treatmentMiceCCR5PLGA NPsPeptide nucleic acidPLGA nanoparticles
2007
Transvascular delivery of small interfering RNA to the central nervous system
Kumar P, Wu H, McBride JL, Jung KE, Hee Kim M, Davidson BL, Kyung Lee S, Shankar P, Manjunath N. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007, 448: 39-43. PMID: 17572664, DOI: 10.1038/nature05901.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBlood-Brain BarrierBrainCell LineDrug Delivery SystemsEncephalitis Virus, JapaneseEncephalitis, JapaneseGene SilencingGenetic VectorsGlycoproteinsGreen Fluorescent ProteinsHeLa CellsHumansLentivirusLiposomesMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODMice, SCIDMolecular Sequence DataNeuronsOligopeptidesRabies virusReceptors, NicotinicRecombinant ProteinsRNA, Small InterferingSuperoxide DismutaseSuperoxide Dismutase-1Viral ProteinsConceptsRVG-9RBlood-brain barrierRabies virus glycoproteinNeuronal cellsTransvascular deliveryFatal viral encephalitisCentral nervous systemTherapeutic moleculesIntravenous treatmentViral encephalitisInflammatory cytokinesAntiviral siRNAIntravenous injectionNervous systemAcetylcholine receptorsNeurological diseasesAnti-peptide antibodiesChimaeric peptidesNoninvasive approachDelivery of siRNABrainSiRNAMiceVirus glycoproteinRobust protection