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
2022
Restriction of viral replication, rather than T cell immunopathology, drives lethality in MNV CR6-infected STAT1-deficient mice
Sharon A, Filyk H, Fonseca N, Simister R, Filler R, Yuen W, Hardman B, Robinson H, Seo J, Rocha-Pereira J, Welch I, Neyts J, Wilen C, Crowe S, Osborne L. Restriction of viral replication, rather than T cell immunopathology, drives lethality in MNV CR6-infected STAT1-deficient mice. The Journal Of Immunology 2022, 208: 182.04-182.04. DOI: 10.4049/jimmunol.208.supp.182.04.Peer-Reviewed Original ResearchAntiviral T cell responsesT cell responsesSTAT1-deficient miceCell responsesViral replicationViral infectionViral-induced tissue damageC57BL6/J miceAdaptive immune populationsLimited viral replicationT cell immunopathologyAdaptive immune cellsUncontrolled viral replicationHigh viral loadHost-directed mechanismKey innateLethal immunopathologyInfectious insultsViral loadImmune populationsImmune cellsJ miceTherapeutic administrationIntestinal homeostasisIntestinal mucosaHigh-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19PatientsRestriction of Viral Replication, Rather than T Cell Immunopathology, Drives Lethality in Murine Norovirus CR6-Infected STAT1-Deficient Mice
Sharon AJ, Filyk HA, Fonseca NM, Simister RL, Filler RB, Yuen W, Hardman BK, Robinson HG, Seo JH, Rocha-Pereira J, Welch I, Neyts J, Wilen CB, Crowe SA, Osborne LC. Restriction of Viral Replication, Rather than T Cell Immunopathology, Drives Lethality in Murine Norovirus CR6-Infected STAT1-Deficient Mice. Journal Of Virology 2022, 96: e02065-21. PMID: 35107369, PMCID: PMC8941907, DOI: 10.1128/jvi.02065-21.Peer-Reviewed Original ResearchConceptsAntiviral T cell responsesT cell responsesSTAT1-deficient miceSystemic viral infectionCell responsesViral replicationViral infectionTissue damageViral-induced tissue damageVirus-induced tissue damageAltered T-cell responsesLimited viral replicationT cell immunopathologyOngoing inflammatory responseAdaptive immune cellsUncontrolled viral replicationBreakdown of toleranceImmune-mediated pathologyHost-directed mechanismViral componentsAntiviral CD4Lethal immunopathologyInfectious insultsImmune activationImmunological tolerance
2021
A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacy
2019
The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon
Grau KR, Zhu S, Peterson ST, Helm EW, Philip D, Phillips M, Hernandez A, Turula H, Frasse P, Graziano VR, Wilen CB, Wobus CE, Baldridge MT, Karst SM. The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon. Nature Microbiology 2019, 5: 84-92. PMID: 31768030, PMCID: PMC6925324, DOI: 10.1038/s41564-019-0602-7.Peer-Reviewed Original ResearchConceptsNorovirus infectionType III interferonsMurine norovirus infectionCommensal bacteriaIII interferonsIntestinal microbiotaType III interferon responseBile acid receptorProximal small intestineRegional expression profilesProximal gutAntibiotic treatmentViral infectionSmall intestineIntestinal tractAcid receptorsInfectionInterferon responseMicrobiotaInterferonPathogenic enteric virusesEnteric virusesHost metabolitesGutExpression profiles
2018
Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection
Orchard RC, Wilen CB, Virgin HW. Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection. Nature Microbiology 2018, 3: 1109-1114. PMID: 30127493, PMCID: PMC6158067, DOI: 10.1038/s41564-018-0221-8.Peer-Reviewed Original ResearchConceptsSerine palmitoyltransferase complexSphingolipid biosynthesisCellular susceptibilityConformational changesLipid biosynthetic enzymesDe novo sphingolipid biosynthesisHost cellular receptorsSerine palmitoyltransferase activityBiosynthetic enzymesBiosynthetic pathwayMurine norovirus infectionMurine norovirusCD300lfCell surfaceBiosynthesisUnappreciated connectionCellular receptorsExtracellular ceramideReceptor conformationViral infectionSurface expressionTarget cell surfaceViral bindingPalmitoyltransferase activityReceptorsTropism for tuft cells determines immune promotion of norovirus pathogenesis
Wilen CB, Lee S, Hsieh LL, Orchard RC, Desai C, Hykes BL, McAllaster MR, Balce DR, Feehley T, Brestoff JR, Hickey CA, Yokoyama CC, Wang YT, MacDuff DA, Kreamalmayer D, Howitt MR, Neil JA, Cadwell K, Allen PM, Handley SA, van Lookeren Campagne M, Baldridge MT, Virgin HW. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 2018, 360: 204-208. PMID: 29650672, PMCID: PMC6039974, DOI: 10.1126/science.aar3799.Peer-Reviewed Original ResearchConceptsVirus infectionImmune promotionTuft cellsType 2 cytokinesEnteric virus infectionEnteric viral infectionsIntestinal epithelial cellsMNoV infectionNorovirus infectionCommensal microbiotaHost immunityViral infectionNorovirus pathogenesisRare typeImmune systemCellular tropismInfectionMouse intestineTarget cellsEpithelial cellsCell proliferationCytokinesTropismCD300lfCells
2017
Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine
Lee S, Wilen CB, Orvedahl A, McCune BT, Kim KW, Orchard RC, Peterson ST, Nice TJ, Baldridge MT, Virgin HW. Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine. Cell Host & Microbe 2017, 22: 449-459.e4. PMID: 28966054, PMCID: PMC5679710, DOI: 10.1016/j.chom.2017.08.021.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsViral surface proteinsCellular tropismPersistent viral infectionNon-structural protein NS1Expression of NS1MNoV infectionSurface proteinsHost cytokinesAntiviral immunityHost determinantsInterferon lambdaViral infectionKey host determinantsViral non-structural proteinsCell tropismFecal sheddingNon-structural proteinsTropism determinantsEpithelial cellsGlobal causeInfectionTropismProtein NS1MNoV