2024
A novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection
Mayer D, Nelson M, Andriyanova D, Filler R, Ökten A, Antao O, Chen J, Scumpia P, Weaver W, Wilen C, Deshayes S, Weinstein J. A novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection. Journal Of Controlled Release 2024, 370: 570-582. PMID: 38734312, DOI: 10.1016/j.jconrel.2024.05.008.Peer-Reviewed Original ResearchAntigen delivery platformGerminal centersCD4<sup>+</sup> T follicular helper (Tfh) cellsT follicular helper (Tfh) cellsAdaptive immune cell responsesOptimal adaptive immune responsesAnti-receptor binding domain antibodiesInfluenza virus challengeRobust neutralizing antibodiesImmune cell responsesEnhanced neutralizing antibodiesAdaptive immune responsesDelivery platformAntibody mediated immunityLymph nodesVaccine platformNeutralizing antibodiesHumoral immunitySARS-CoV-2 spike proteinSustained release profileTarget antigenImmune responseVirus challengeViral infectionCell responses
2023
Game over for RSV?
Strine M, Wilen C. Game over for RSV? Science Immunology 2023, 8: eadi8764. PMID: 37276355, PMCID: PMC11528347, DOI: 10.1126/sciimmunol.adi8764.Commentaries, Editorials and LettersAge-associated features of norovirus infection analysed in mice
Kennedy E, Aggarwal S, Dhar A, Karst S, Wilen C, Baldridge M. Age-associated features of norovirus infection analysed in mice. Nature Microbiology 2023, 8: 1095-1107. PMID: 37188813, PMCID: PMC10484054, DOI: 10.1038/s41564-023-01383-1.Peer-Reviewed Original ResearchConceptsViral uptakeWild-type neonatal miceCortisone acetate administrationAdaptive immune responsesInterferon-stimulated gene expressionIntestinal tuft cellsSeverity of infectionAbsence of interferonAge-associated variabilityAge-associated featuresMNoV infectionAcetate administrationViral exposureAntibody responseEnteric infectionsNeonatal miceInfected damsNorovirus infectionHigh burdenImmune responsePersistent infectionViral RNA accumulationIleal absorptionJuvenile miceAdult mice
2022
Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species
Peng L, Fang Z, Renauer PA, McNamara A, Park JJ, Lin Q, Zhou X, Dong MB, Zhu B, Zhao H, Wilen CB, Chen S. Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species. Cell Reports 2022, 40: 111160. PMID: 35921835, PMCID: PMC9294034, DOI: 10.1016/j.celrep.2022.111160.Peer-Reviewed Original ResearchConceptsAntibody responseCoronavirus speciesSequential vaccinationSARS-CoVAntigen-specific antibody responsesSARS-CoV-2 DeltaAdaptive immune cellsEffective immune responsePotent antibody responsesCOVID-19 vaccineSARS-CoV-2MRNA vaccine candidatesActivated B cellsSingle-cell RNA sequencing profilesRNA sequencing profilesSimultaneous vaccinationAntibody immunityVaccination scheduleImmune profileImmune cellsImmune responseVaccine candidatesMERS-CoV.Animal modelsB cellsDefining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency
Shin JJ, Par-Young J, Unlu S, McNamara A, Park HJ, Shin MS, Gee RJ, Doyle H, Afinogenova Y, Zidan E, Kwah J, Russo A, Mamula M, Hsu FI, Catanzaro J, Racke M, Bucala R, Wilen C, Kang I. Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency. Journal Of Clinical Immunology 2022, 42: 1137-1150. PMID: 35713752, PMCID: PMC9203263, DOI: 10.1007/s10875-022-01296-4.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralCD8-Positive T-LymphocytesCommon Variable ImmunodeficiencyCOVID-19COVID-19 VaccinesHumansImmunity, CellularImmunoglobulin AImmunoglobulin GMRNA VaccinesPrimary Immunodeficiency DiseasesRNA, MessengerSARS-CoV-2Spike Glycoprotein, CoronavirusVaccinationVaccinesVaccines, SyntheticConceptsCommon variable immune deficiencyT cellsImmune responseIgG responsesCVID patientsMRNA vaccinesB cellsCoronavirus disease 2019 (COVID-19) mRNA vaccinesCOVID-19 mRNA vaccinesBaseline immune profileHistory of autoimmunityPrimary antibody deficiencyT cell responsesCellular immune responsesPoor immune responseVariable immune deficiencyMemory B cellsSARS-CoV-2 spike proteinBaseline IgGCVID diagnosisEM CD8Immunological predictorsPAD cohortSpecific CD4Immune profileVariant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2
Peng L, Renauer PA, Ökten A, Fang Z, Park JJ, Zhou X, Lin Q, Dong MB, Filler R, Xiong Q, Clark P, Lin C, Wilen CB, Chen S. Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2. Cell Reports Medicine 2022, 3: 100634. PMID: 35561673, PMCID: PMC9040489, DOI: 10.1016/j.xcrm.2022.100634.Peer-Reviewed Original ResearchConceptsImmune responseImmune cell populationsSARS-CoV-2 spikeAssessment of efficacySARS-CoV-2LNP-mRNABreakthrough infectionsCD8 TImmune profilingMRNA vaccinesPotent protectionT lymphocytesNeutralization activityDelta variantAnimal modelsPotent antibodiesRepertoire diversityCell responsesAuthentic virusSystemic increaseVariant lineagesClonal expansionCell populationsCOVID-19VaccinationTuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces
Strine MS, Wilen CB. Tuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces. PLOS Pathogens 2022, 18: e1010318. PMID: 35271673, PMCID: PMC8912186, DOI: 10.1371/journal.ppat.1010318.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInterkingdom interactionsTuft cellsCell biologyImmune responseMicrobial activationMicrobial sensingCell abundanceMucosal barrier surfacesAntiviral adaptive immune responsesType 2 immune responsesCell heterogeneityExquisite specificityMucosal barrier integrityAdaptive immune responsesMurine norovirusHuman healthKey orchestratorsMicrobial infectionsPathogenic bacteriaBroad intraFlavivirus replicationKey mediatorContext of coinfectionTissue repairImmune evasion
2021
Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein
Hsu JC, Laurent-Rolle M, Pawlak JB, Wilen CB, Cresswell P. Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2101161118. PMID: 34045361, PMCID: PMC8214666, DOI: 10.1073/pnas.2101161118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Interferon-stimulated genesImmune responseSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Host protein synthesisRespiratory syndrome coronavirus 2Syndrome coronavirus 2Innate immune responseUnprecedented global health crisisCoronavirus 2N7-methyltransferase activityOngoing COVID-19 pandemicHuman coronavirusesTranslational shutdownVirus replicationNsp14 proteinGlobal health crisisProtein synthesisInhibition activityCausative agentCOVID-19COVID-19 pandemicSARS-CoV-2 nsp14Dependent inductionCD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus
Graziano VR, Alfajaro MM, Schmitz CO, Filler RB, Strine MS, Wei J, Hsieh LL, Baldridge MT, Nice TJ, Lee S, Orchard RC, Wilen CB. CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. Journal Of Virology 2021, 95: 10.1128/jvi.01652-20. PMID: 33177207, PMCID: PMC7925115, DOI: 10.1128/jvi.01652-20.Peer-Reviewed Original ResearchConceptsConditional knockout miceIntestinal epithelial cellsCell tropismKnockout miceTuft cellsDendritic cellsMyelomonocytic cellsB cellsCellular tropismMurine norovirusEpithelial cellsViral RNA levelsInnate immune responseCause of gastroenteritisMNoV infectionCell typesViral loadGastrointestinal infectionsReceptor expressionImmunocompetent humansImmune responseCell type-specific rolesMouse modelIntestinal tissueMNoVNonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection
Chen JS, Alfajaro MM, Chow RD, Wei J, Filler RB, Eisenbarth SC, Wilen CB. Nonsteroidal Anti-inflammatory Drugs Dampen the Cytokine and Antibody Response to SARS-CoV-2 Infection. Journal Of Virology 2021, 95: 10.1128/jvi.00014-21. PMID: 33441348, PMCID: PMC8092681, DOI: 10.1128/jvi.00014-21.Peer-Reviewed Original ResearchSARS-CoV-2 infectionNonsteroidal anti-inflammatory drugsCOVID-19 pathogenesisSARS-CoV-2Anti-inflammatory drugsProduction of prostaglandinsCyclooxygenase-2Immune responseNSAID treatmentCyclooxygenase-1Enzymes cyclooxygenase-1Inflammatory responseAbility of NSAIDsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionSARS-CoV-2 vaccinationViral replicationPro-inflammatory cytokine responseCoronavirus 2 infectionExpression of angiotensinRelief of painPro-inflammatory cytokinesCoronavirus disease 2019 (COVID-19) pandemicHumoral immune response
2020
UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages
Balce DR, Wang YT, McAllaster MR, Dunlap BF, Orvedahl A, Hykes BL, Droit L, Handley SA, Wilen CB, Doench JG, Orchard RC, Stallings CL, Virgin HW. UFMylation inhibits the proinflammatory capacity of interferon-γ–activated macrophages. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2011763118. PMID: 33372156, PMCID: PMC7817147, DOI: 10.1073/pnas.2011763118.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPR knockout screenCRISPR knockout screensEndoplasmic reticulum stress responseRegulation of responsesReticulum stress responseKnockout screensTranscriptional responseGenetic roadmapIFN-γ responsesTumor necrosis factorNegative regulatorMolecular linkUfmylation pathwayUnexpected roleStress responseMacrophage cell lineIFN-γ activationIntracellular pathogensProinflammatory capacityConjugation systemInfluenza infectionCellular immunityIFN-γ effectsNecrosis factorImmune response
2012
HIV: Cell Binding and Entry
Wilen CB, Tilton JC, Doms RW. HIV: Cell Binding and Entry. Cold Spring Harbor Perspectives In Medicine 2012, 2: a006866. PMID: 22908191, PMCID: PMC3405824, DOI: 10.1101/cshperspect.a006866.Peer-Reviewed Original ResearchConceptsHIV entryViral tropismPrimary cellular receptor CD4Human immunodeficiency virus (HIV) replicationAbility of HIVImmunodeficiency virus replicationHost immune responseHuman immune systemCellular receptor CD4Immune responseCellular coreceptorTherapeutic interventionsImmune systemReceptor CD4Virus replicationHIVCell bindingHost cell cytoplasmTropismHost cell membraneTrigger fusionCell cytoplasmCD4Major rolePathogenesis
2011
Molecular Mechanisms of HIV Entry
Wilen CB, Tilton JC, Doms RW. Molecular Mechanisms of HIV Entry. Advances In Experimental Medicine And Biology 2011, 726: 223-242. PMID: 22297516, DOI: 10.1007/978-1-4614-0980-9_10.Peer-Reviewed Original ResearchConceptsHIV entryOnly viral surface proteinHuman immunodeficiency virus (HIV) entryHumoral immune responseMembrane fusion machineryCoreceptor-binding siteHost protein CD4Viral surface proteinsHIV infectionSmall molecule inhibitorsImmune responseChemokine coreceptorsFusion machineryViral tropismClinical treatmentVirus entryMolecular mechanismsHost cellsFacilitates exposureMolecule inhibitorsGp41 subunitSurface proteinsViral genomeAmino acidsCD4