2022
Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses
Mao T, Israelow B, Peña-Hernández MA, Suberi A, Zhou L, Luyten S, Reschke M, Dong H, Homer RJ, Saltzman WM, Iwasaki A. Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses. Science 2022, 378: eabo2523. PMID: 36302057, PMCID: PMC9798903, DOI: 10.1126/science.abo2523.Peer-Reviewed Original ResearchConceptsRespiratory mucosaSystemic immunityLethal SARS-CoV-2 infectionAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicSARS-CoV-2 infectionProtective mucosal immunityCross-reactive immunityT cell responsesCoronavirus 2 pandemicPrimary vaccinationParenteral vaccinesMucosal immunityVaccine strategiesRespiratory tractImmunoglobulin AMemory BImmune memoryPartial immunityCell responsesPoor immunityImmunitySpike proteinMucosaVaccineEndogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease
Jayewickreme R, Mao T, Philbrick W, Kong Y, Treger RS, Lu P, Rakib T, Dong H, Dang-Lawson M, Guild WA, Lau TJ, Iwasaki A, Tokuyama M. Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease. Frontiers In Immunology 2022, 12: 758721. PMID: 35058919, PMCID: PMC8764156, DOI: 10.3389/fimmu.2021.758721.Peer-Reviewed Original ResearchConceptsHSV-2 infectionHSV-2 diseaseHerpes simplex virus type 2 infectionSimplex virus type 2 infectionEnhanced type I interferonIntravaginal HSV-2 infectionVaginal HSV-2 infectionVirus type 2 infectionEndogenous retrovirusesReceptor-deficient miceType 2 infectionHigh systemic levelsWildtype C57BL/6 miceType I interferonTLR7-/- miceC57BL/6 miceInfectious endogenous retrovirusDeficient miceIntravaginal applicationAntiviral immunityI interferonVaginal tissueDetrimental functionsTLR7Mice
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
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMiceVEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Song E, Mao T, Dong H, Boisserand LSB, Antila S, Bosenberg M, Alitalo K, Thomas JL, Iwasaki A. VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 2020, 577: 689-694. PMID: 31942068, PMCID: PMC7100608, DOI: 10.1038/s41586-019-1912-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCD8-Positive T-LymphocytesCell Cycle CheckpointsCell Line, TumorCell MovementCentral Nervous SystemCross-PrimingFemaleGlioblastomaHEK293 CellsHumansImmunologic MemoryImmunologic SurveillanceLymph NodesLymphangiogenesisLymphatic VesselsMaleMelanomaMeningesMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor CConceptsCD8 T cellsCentral nervous systemT cellsImmune responseBrain tumorsImmune surveillanceLymphatic drainageNervous systemAntigen-specific immune responsesDeep cervical lymph nodesCapacity of VEGFCervical lymph nodesCheckpoint blockade therapyMeningeal lymphatic systemVascular endothelial growth factor CNew therapeutic approachesUncontrolled tumor growthMeningeal lymphatic vasculatureBlockade therapyLymph nodesTherapeutic approachesMouse modelTumor growthMemory responsesTumors
2019
Human APOBEC3G Prevents Emergence of Infectious Endogenous Retrovirus in Mice
Treger RS, Tokuyama M, Dong H, Salas-Briceno K, Ross SR, Kong Y, Iwasaki A. Human APOBEC3G Prevents Emergence of Infectious Endogenous Retrovirus in Mice. Journal Of Virology 2019, 93: 10.1128/jvi.00728-19. PMID: 31341050, PMCID: PMC6798113, DOI: 10.1128/jvi.00728-19.Peer-Reviewed Original ResearchConceptsToll-like receptor 7Infectious endogenous retrovirusHuman APOBEC3GAPOBEC3GHA3GEndogenous retrovirusesAntiviral restriction factorsReceptor 7Human endogenous retrovirusesTransgenic miceERV RNAsERV reactivationMiceAPOBEC3 proteinsCell-intrinsic defenseHost mechanismsPrevents emergenceRestriction factorsPermissive cellsDeleterious consequencesSubsequent disruptionRetrovirusesEctopic expressionHumansExpression
2016
Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza