Featured Publications
Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
Sparks R, Lau W, Liu C, Han K, Vrindten K, Sun G, Cox M, Andrews S, Bansal N, Failla L, Manischewitz J, Grubbs G, King L, Koroleva G, Leimenstoll S, Snow L, Chen J, Tang J, Mukherjee A, Sellers B, Apps R, McDermott A, Martins A, Bloch E, Golding H, Khurana S, Tsang J. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature 2023, 614: 752-761. PMID: 36599369, PMCID: PMC10481789, DOI: 10.1038/s41586-022-05670-5.Peer-Reviewed Original ResearchConceptsMild COVID-19Control individualsInnate immune genesInfluenza vaccinationCOVID-19Day 28Day 1Viral infectionNon-hospitalized COVID-19Baseline immune statusAcute viral infectionSex-matched control individualsMemory-like CD8IL-15 responsesIL-15 stimulationSex-dimorphic effectsToll-like receptorsFuture immune responseHealthy control individualsImmune genesSystems immunology approachT-cell activation signaturesHealthy male individualsMale individualsMore IFNγBroad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus
Kotliarov Y, Sparks R, Martins A, Mulè M, Lu Y, Goswami M, Kardava L, Banchereau R, Pascual V, Biancotto A, Chen J, Schwartzberg P, Bansal N, Liu C, Cheung F, Moir S, Tsang J. Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus. Nature Medicine 2020, 26: 618-629. PMID: 32094927, PMCID: PMC8392163, DOI: 10.1038/s41591-020-0769-8.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdolescentAdultAgedAged, 80 and overAntibody FormationB-LymphocytesChildChild, PreschoolCohort StudiesFemaleGene Expression ProfilingHumansInfluenza VaccinesInfluenza, HumanLupus Erythematosus, SystemicMaleMiddle AgedTranscriptomeVaccinationYellow FeverYellow Fever VaccineYoung AdultConceptsDisease activityVaccine responsivenessAutoimmune disease activityBlood transcriptional signaturesYellow fever vaccinationSystemic lupus erythematosusClinical quiescenceFever vaccinationLupus erythematosusCancer immunotherapyBaseline predictorsDisease outcomeHealthy subjectsImmune responseI IFNHealthy individualsVaccinationTranscriptional signatureImmune variationBaseline statePatientsExtent of activationBiological basisSurface proteinsInfection responseSystematic Analysis of Cell-to-Cell Expression Variation of T Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations
Lu Y, Biancotto A, Cheung F, Remmers E, Shah N, McCoy J, Tsang J. Systematic Analysis of Cell-to-Cell Expression Variation of T Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations. Immunity 2016, 45: 1162-1175. PMID: 27851916, PMCID: PMC6532399, DOI: 10.1016/j.immuni.2016.10.025.Peer-Reviewed Original ResearchConceptsExpression variationDisease-associated genetic polymorphismsSingle-cell dataPrimary cell populationsCell populationsOrganismal levelFunctional associationDisease susceptibilityGenetic associationFlow cytometry dataCytometry dataGenetic polymorphismsHuman cohortsFlow cytometryCellsHigh-dimensional flow cytometryCell subpopulationsImportant rolePrevalent featureProteinPhenotypeSystematic analysisMultiple baseline measurementsPolymorphismPopulationGlobal Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses
Tsang J, Schwartzberg P, Kotliarov Y, Biancotto A, Xie Z, Germain R, Wang E, Olnes M, Narayanan M, Golding H, Moir S, Dickler H, Perl S, Cheung F, Center T, Consortium T, Obermoser G, Chaussabel D, Palucka K, Chen J, Fuchs J, Ho J, Khurana S, King L, Langweiler M, Liu H, Manischewitz J, Pos Z, Posada J, Schum P, Shi R, Valdez J, Wang W, Zhou H, Kastner D, Marincola F, McCoy J, Trinchieri G, Young N. Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses. Cell 2014, 157: 499-513. PMID: 24725414, PMCID: PMC4139290, DOI: 10.1016/j.cell.2014.03.031.Peer-Reviewed Original ResearchConceptsPre-existing antibody titersPostvaccination antibody responsePeripheral blood mononuclear cell transcriptomeB cell responsesBaseline time pointPostvaccination responsesInfluenza vaccinationImmune monitoringSerum titersAntibody titersAntibody responseBaseline predictorsBaseline differencesImmune parametersHuman immunityCell responsesSubpopulation frequenciesTime pointsCell populationsIntra-individual variationVaccinationTiters
2023
Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine
Cheung F, Apps R, Dropulic L, Kotliarov Y, Chen J, Jordan T, Langweiler M, Candia J, Biancotto A, Han K, Rachmaninoff N, Pietz H, Wang K, Tsang J, Cohen J. Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine. ELife 2023, 12: e80652. PMID: 36648132, PMCID: PMC9844983, DOI: 10.7554/elife.80652.Peer-Reviewed Original ResearchConceptsEarly innate responseVaccine recipientsPrior exposureInnate responseType I interferon signatureInfectious diseasesSeronegative vaccine recipientsType I IFN responseEarly antiviral responseNational InstituteInnate immune responseSystems immunology approachI IFN responseAdaptive immune phenotypesIntramural Research ProgramInterferon signatureAntibody titersVaccine trialsImmune phenotypeVirus vaccineNaive womenImmune responseSanofi PasteurDay 1Herpesvirus vaccine
2020
Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells
Baharom F, Ramirez-Valdez RA, Tobin KKS, Yamane H, Dutertre CA, Khalilnezhad A, Reynoso GV, Coble VL, Lynn GM, Mulè MP, Martins AJ, Finnigan JP, Zhang XM, Hamerman JA, Bhardwaj N, Tsang JS, Hickman HD, Ginhoux F, Ishizuka AS, Seder RA. Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells. Nature Immunology 2020, 22: 41-52. PMID: 33139915, PMCID: PMC7746638, DOI: 10.1038/s41590-020-00810-3.Peer-Reviewed Original ResearchConceptsNeoantigen-specific CD8T cellsToll-like receptor 7/8 agonistQuality of CD8Stem-like TCF1T cell immunityStem-like CD8Superior antitumor responsesPersonalized cancer vaccinesStem-like genesStem-like cellsIntravenous vaccinationNanoparticle vaccinationAntitumor immunityCheckpoint blockadeCell immunityDendritic cellsAntitumor responseEffector cellsSubcutaneous immunizationCancer vaccinesVaccine parametersNeoantigen peptidesAntigen presentationNanoparticle vaccine
2019
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
Austin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Science Translational Medicine 2019, 11 PMID: 31776286, PMCID: PMC7479651, DOI: 10.1126/scitranslmed.aax0904.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, NeutralizingAntibody AffinityAntigens, CD19B-LymphocytesCytokinesFemaleGerminal CenterHIV InfectionsHumansImmunologic MemoryLymph NodesMaleMiddle AgedMutation RatePhenotypeReceptors, Antigen, B-CellT-Box Domain ProteinsT-Lymphocytes, Helper-InducerTranscriptomeYoung AdultConceptsHIV-specific B cellsT-betGC B cellsGerminal centersB cellsLymph nodesPoor affinity maturationChronic immune activationMemory B cell compartmentAntibody-mediated immunityChronic infectious diseaseOptimal antibody responseB cell compartmentChronic human infectionsB cell receptorHIV viremiaImmunologic outcomesHIV infectionViremic individualsChronic viremiaImmune activationPeripheral bloodProtective antibodiesAntibody responseCD19