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 responseCancer prognosis with shallow tumor RNA sequencing
Milanez-Almeida P, Martins A, Germain R, Tsang J. Cancer prognosis with shallow tumor RNA sequencing. Nature Medicine 2020, 26: 188-192. PMID: 32042193, DOI: 10.1038/s41591-019-0729-3.Peer-Reviewed Original ResearchConceptsCancer prognosisTumor RNA-seq dataTumor RNA sequencingPrediction of outcomeTypes of cancerClinical outcomesRNA sequencingAdverse outcomesRelative riskDisease outcomeOutcome predictionTumor RNA-seqPersonalized oncologyTranscriptional signatureCancer1–3Molecular pathwaysOutcomesPrognosisLongitudinal analysisTranscriptional pathwaysCancerSystematic 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 measurementsPolymorphismPopulationA crowdsourcing approach for reusing and meta-analyzing gene expression data
Shah N, Guo Y, Wendelsdorf K, Lu Y, Sparks R, Tsang J. A crowdsourcing approach for reusing and meta-analyzing gene expression data. Nature Biotechnology 2016, 34: 803-806. PMID: 27323300, PMCID: PMC6871002, DOI: 10.1038/nbt.3603.Peer-Reviewed Original ResearchUtilizing population variation, vaccination, and systems biology to study human immunology
Tsang J. Utilizing population variation, vaccination, and systems biology to study human immunology. Trends In Immunology 2015, 36: 479-493. PMID: 26187853, PMCID: PMC4979540, DOI: 10.1016/j.it.2015.06.005.Peer-Reviewed Original ResearchGlobal 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 variationVaccinationTitersIntegrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint
Mulè M, Martins A, Cheung F, Farmer R, Sellers B, Quiel J, Jain A, Kotliarov Y, Bansal N, Chen J, Schwartzberg P, Tsang J. Integrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint. Immunity 2024, 57: 1160-1176.e7. PMID: 38697118, DOI: 10.1016/j.immuni.2024.04.009.Peer-Reviewed Original ResearchConceptsTranscriptional statesVaccine responseSingle-cell profiling methodsSingle-cell variationAS03-adjuvanted vaccineUnadjuvanted influenza vaccineResponse to lipopolysaccharide stimulationB cell signaturesCD14<sup>+</sup> monocytesSingle-cell levelBiological insightsUnadjuvanted vaccineAS03-adjuvantedInfluenza vaccineResponse phenotypesCITE-seqInnate subsetsAdjuvant developmentHigh antibody respondersDay 1Antibody respondersLipopolysaccharide stimulationVaccineCorrelation networkHuman populationImproving Vaccine-Induced Immunity: Can Baseline Predict Outcome?
Tsang J, Dobaño C, VanDamme P, Moncunill G, Marchant A, Othman R, Sadarangani M, Koff W, Kollmann T. Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome? Trends In Immunology 2020, 41: 457-465. PMID: 32340868, PMCID: PMC7142696, DOI: 10.1016/j.it.2020.04.001.Peer-Reviewed Original Research
2023
Systems immunology of regulatory T cells: can one circuit explain it all?
Tripathi S, Tsang J, Park K. Systems immunology of regulatory T cells: can one circuit explain it all? Trends In Immunology 2023, 44: 766-781. PMID: 37690962, PMCID: PMC10543564, DOI: 10.1016/j.it.2023.08.007.Peer-Reviewed Original ResearchTracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine
de Assis F, Hoehn K, Zhang X, Kardava L, Smith C, Merhebi O, Buckner C, Trihemasava K, Wang W, Seamon C, Chen V, Schaughency P, Cheung F, Martins A, Chiang C, Li Y, Tsang J, Chun T, Kleinstein S, Moir S. Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine. Cell Reports 2023, 42: 112780. PMID: 37440409, PMCID: PMC10529190, DOI: 10.1016/j.celrep.2023.112780.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell receptorB cellsAtypical memory B cellsInfection-naïve individualsTwo-dose SARSSARS-CoV-2 mRNAB cell responsesAntibody-secreting cellsMonth 6Protective immunityCell responsesCell receptorClonal expansionImmunoglobulin GEarly timepointsLater timepointsPlasmablastsVaccinationCD71TimepointsSurface proteinsCellsMultimodal single-cell analysisMRNASex 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
2022
Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children
Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Oguz C, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Kitakule M, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, McGuire P, Pittaluga S, Germain R, Apps R, Schwartz D, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P, Manthiram K. Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children. Nature Immunology 2022, 24: 186-199. PMID: 36536106, PMCID: PMC10777159, DOI: 10.1038/s41590-022-01367-z.Peer-Reviewed Original ResearchConceptsT cell receptorImmune responseGerminal centersPrevious SARS-CoV-2 infectionSARS-CoV-2 infectionB-cell receptor sequencingTissue-specific immunityCell receptor sequencingAdaptive immune responsesUpper respiratory tractMemory B cellsT cell clonotypesSite of infectionSARS-CoV-2Pharyngeal lymphoid tissuePeripheral bloodLymphocyte populationsLymphoid tissueRespiratory tractCell clonotypesAdaptive immunityB cellsCDR3 sequencesAdenoidsCell receptorTranscriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses
Hagan T, Gerritsen B, Tomalin LE, Fourati S, Mulè MP, Chawla DG, Rychkov D, Henrich E, Miller HER, Diray-Arce J, Dunn P, Lee A, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Sékaly R, Kleinstein S, Pulendran B. Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses. Nature Immunology 2022, 23: 1788-1798. PMID: 36316475, PMCID: PMC9869360, DOI: 10.1038/s41590-022-01328-6.Peer-Reviewed Original ResearchConceptsAntibody responseDay 1Vaccine-induced antibodiesYellow fever vaccineHuman immune responseMechanisms of immunityB cell activationTranscriptional atlasFever vaccineDifferent vaccinesSystems vaccinologyImmune responseMost vaccinesDay 7Cell activationInnate immunityVaccineVaccinationImmunityCommon predictorsMolecular signaturesResponsePlasmablastsInterferonAntibodiesPan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Fourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination. Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.Peer-Reviewed Original ResearchConceptsAntibody responsePro-inflammatory response genesToll-like receptor ligandsBlood transcriptional profilesHigher serum antibodyPro-inflammatory responseSerum antibodiesDifferent vaccinesImmune responseImmune stateMetabolism alterationsEndotypesImmune systemVaccinationReceptor ligandsCell proliferationGene expression characteristicsActivation stateDifferential expressionTranscriptional profilesResponse genesExpression characteristicsResponseWide variationAdjuvantThe Immune Signatures data resource, a compendium of systems vaccinology datasets
Diray-Arce J, Miller HER, Henrich E, Gerritsen B, Mulè MP, Fourati S, Gygi J, Hagan T, Tomalin L, Rychkov D, Kazmin D, Chawla DG, Meng H, Dunn P, Campbell J, Sarwal M, Tsang J, Levy O, Pulendran B, Sekaly R, Floratos A, Gottardo R, Kleinstein S, Suárez-Fariñas M. The Immune Signatures data resource, a compendium of systems vaccinology datasets. Scientific Data 2022, 9: 635. PMID: 36266291, PMCID: PMC9584267, DOI: 10.1038/s41597-022-01714-7.Peer-Reviewed Original ResearchConceptsHuman Immunology Project ConsortiumDifferent vaccinesCost-effective public health interventionsGene Expression OmnibusInfection-induced morbiditySystems immunology approachPublic health interventionsMultiple relevant studiesVaccine responsesHealth interventionsVaccineRelevant studiesVaccine discoveryUnderstanding of mechanismsMolecular signaturesImmPortSystems immunologyImmunologyStudy dataTraditional immunologyMorbidityCohortImmunogenicityMortalityReleaseConsidering innate immune responses in SARS-CoV-2 infection and COVID-19
Diamond M, Lambris J, Ting J, Tsang J. Considering innate immune responses in SARS-CoV-2 infection and COVID-19. Nature Reviews Immunology 2022, 22: 465-470. PMID: 35788185, PMCID: PMC9252555, DOI: 10.1038/s41577-022-00744-x.Peer-Reviewed Original ResearchEarly human B cell signatures of the primary antibody response to mRNA vaccination
Kardava L, Rachmaninoff N, Lau W, Buckner C, Trihemasava K, Blazkova J, de Assis F, Wang W, Zhang X, Wang Y, Chiang C, Narpala S, McCormack G, Liu C, Seamon C, Sneller M, O’Connell S, Li Y, McDermott A, Chun T, Fauci A, Tsang J, Moir S. Early human B cell signatures of the primary antibody response to mRNA vaccination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2204607119. PMID: 35759653, PMCID: PMC9282446, DOI: 10.1073/pnas.2204607119.Peer-Reviewed Original ResearchConceptsMemory B cellsAntibody responseDose 2MBC populationsB cellsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Durability of antibodiesSubsequent antibody levelsB cell signaturesIgG antibody responsePrimary antibody responseSyndrome coronavirus 2Weak antibody responseMessenger RNA vaccinesPlasmablast frequencyFirst doseMRNA vaccinationMonth 6Antibody levelsProtective immunitySecond dosesAntibody titersCoronavirus 2Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
Sacco K, Castagnoli R, Vakkilainen S, Liu C, Delmonte OM, Oguz C, Kaplan IM, Alehashemi S, Burbelo PD, Bhuyan F, de Jesus AA, Dobbs K, Rosen LB, Cheng A, Shaw E, Vakkilainen MS, Pala F, Lack J, Zhang Y, Fink DL, Oikonomou V, Snow AL, Dalgard CL, Chen J, Sellers BA, Montealegre Sanchez GA, Barron K, Rey-Jurado E, Vial C, Poli MC, Licari A, Montagna D, Marseglia GL, Licciardi F, Ramenghi U, Discepolo V, Lo Vecchio A, Guarino A, Eisenstein EM, Imberti L, Sottini A, Biondi A, Mató S, Gerstbacher D, Truong M, Stack MA, Magliocco M, Bosticardo M, Kawai T, Danielson JJ, Hulett T, Askenazi M, Hu S, Cohen J, Su H, Kuhns D, Lionakis M, Snyder T, Holland S, Goldbach-Mansky R, Tsang J, Notarangelo L. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nature Medicine 2022, 28: 1050-1062. PMID: 35177862, PMCID: PMC9119950, DOI: 10.1038/s41591-022-01724-3.Peer-Reviewed Original ResearchConceptsInflammatory syndromeSevere acute respiratory syndrome coronavirus 2Pediatric coronavirus disease 2019Acute respiratory syndrome coronavirus 2Robust type I interferon (IFN) responseRespiratory syndrome coronavirus 2Pediatric COVID-19Pediatric healthy controlsSignatures of inflammationMultisystem inflammatory syndromeTime of admissionSyndrome coronavirus 2Combination of HLAT cell clonotypesType I interferon responseCoronavirus disease 2019Multi-institutional studyCOVID-19Minority of childrenT cell activationI interferon responseType II IFNSubstantial morbidityCoronavirus 2PCR status
2021
Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19