Featured Publications
Maturation of germinal center B cells after influenza virus vaccination in humans
McIntire K, Meng H, Lin T, Kim W, Moore N, Han J, McMahon M, Wang M, Malladi S, Mohammed B, Zhou J, Schmitz A, Hoehn K, Carreño J, Yellin T, Suessen T, Middleton W, Teefey S, Presti R, Krammer F, Turner J, Ward A, Wilson I, Kleinstein S, Ellebedy A. Maturation of germinal center B cells after influenza virus vaccination in humans. Journal Of Experimental Medicine 2024, 221: e20240668. PMID: 38935072, PMCID: PMC11211068, DOI: 10.1084/jem.20240668.Peer-Reviewed Original ResearchConceptsB cellsInfluenza vaccineGerminal centersAntigen-specific GC B cellsResponse to seasonal influenza vaccinationLong-lived bone marrow plasma cellsResponse to influenza vaccinationBone marrow plasma cellsGerminal center B cellsGC B cell clonesInfluenza virus vaccineMaturation of B cellsMarrow plasma cellsSeasonal influenza vaccineMemory B cellsHemagglutinin (HAB cell clonesGC B cellsInfluenza hemagglutinin (HAH5 HANeedle aspirationLymphoid structuresLymph nodesPlasma cellsGC reaction
2023
Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre N, Lutz R, Cruz I, Raddassi K, Ruff W, Racke M, Wilson J, Givens T, Grifoni A, Weiskopf D, Sette A, Kleinstein S, Montgomery R, Shaw A, Li F, Fan R, Hafler D, Tomayko M, Longbrake E. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023, 8: e168102. PMID: 37606046, PMCID: PMC10543713, DOI: 10.1172/jci.insight.168102.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinationB-cell-depleted patientsB-cell depletionAntibody responseMRNA vaccinationThird doseCell depletionT cellsClaude D. Pepper Older Americans Independence CenterB cellsNational Multiple Sclerosis SocietyAnti-CD20 antibodySpike-specific antibodiesMultiple Sclerosis SocietyLow cumulative exposureLogistic regression modelsImportant clinical needCD20 therapyCD20 treatmentMost patientsThird vaccineSerologic responseVaccine dosesMRNA vaccinesVaccination strategiesPredictive overfitting in immunological applications: Pitfalls and solutions
Gygi J, Kleinstein S, Guan L. Predictive overfitting in immunological applications: Pitfalls and solutions. Human Vaccines & Immunotherapeutics 2023, 19: 2251830. PMID: 37697867, PMCID: PMC10498807, DOI: 10.1080/21645515.2023.2251830.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 analysisMRNAHigh-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults
Wang M, Jiang R, Mohanty S, Meng H, Shaw A, Kleinstein S. High-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults. Aging 2023, 15: 9250-9274. PMID: 37367734, PMCID: PMC10564424, DOI: 10.18632/aging.204778.Peer-Reviewed Original ResearchConceptsB cellsActivated B cellsB cell receptorOlder adultsInfluenza vaccinationAge groupsPeripheral blood B cellsYoung adultsInactivated influenza vaccineB cell responsesSubstantial disease burdenBlood B cellsMemory B cellsInfluenza vaccination responsesStrong antibody responseAge-related changesInfluenza vaccineVaccination responseSeasonal influenzaAntibody responseHospital visitsDisease burdenSomatic hypermutation frequenciesVaccinationCell responsesPlatelet response to influenza vaccination reflects effects of aging
Konstorum A, Mohanty S, Zhao Y, Melillo A, Vander Wyk B, Nelson A, Tsang S, Blevins T, Belshe R, Chawla D, Rondina M, Gill T, Montgomery R, Allore H, Kleinstein S, Shaw A. Platelet response to influenza vaccination reflects effects of aging. Aging Cell 2023, 22: e13749. PMID: 36656789, PMCID: PMC9924941, DOI: 10.1111/acel.13749.Peer-Reviewed Original ResearchConceptsCommunity-dwelling older adultsPlatelet activationOlder adultsInfluenza vaccinationAge-associated chronic inflammationInfluence platelet functionRNA expressionPro-inflammatory diseasesAge-associated increasePlatelet activation pathwaysAge-associated differencesActivation pathwayPlatelet transcriptomeGeriatric conditionsChronic inflammationImmune responsePlatelet functionPlatelet responseSNF residentsVaccinationActivation responseYoung individualsProtein levelsAdultsYounger participants
2022
A curated collection of human vaccination response signatures
Smith K, Chawla D, Dhillon B, Ji Z, Vita R, van der Leest E, Weng J, Tang E, Abid A, Peters B, Hancock R, Floratos A, Kleinstein S. A curated collection of human vaccination response signatures. Scientific Data 2022, 9: 678. PMID: 36347894, PMCID: PMC9643367, DOI: 10.1038/s41597-022-01558-1.Peer-Reviewed Original ResearchTranscriptional 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 ResearchMeSH KeywordsAdultAntibodies, ViralAntibody FormationGene Expression ProfilingHumansImmunity, InnateVaccinationVaccinesConceptsAntibody 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 variationAdjuvant
2021
Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving
Hoehn KB, Turner JS, Miller FI, Jiang R, Pybus OG, Ellebedy A, Kleinstein SH. Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving. ELife 2021, 10: e70873. PMID: 34787567, PMCID: PMC8741214, DOI: 10.7554/elife.70873.Peer-Reviewed Original ResearchConceptsSeasonal influenza vaccinationInfluenza vaccinationB-cell lineageGerminal centersB cell evolutionPoor efficacyB cellsSeasonal influenza virus vaccinationSeasonal influenza virus vaccinesVaccine-induced B cell responsesInfluenza virus vaccinationInfluenza virus vaccinePre-existing immunityB cell responsesMemory B cellsCell lineagesGC B cellsSeasonal vaccinationHIV infectionVirus vaccinationVirus vaccineVaccinationVaccine antigensCell responsesSignificant heterogeneity
2020
CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response
Lu Y, Jiang R, Freyn AW, Wang J, Strohmeier S, Lederer K, Locci M, Zhao H, Angeletti D, O’Connor K, Kleinstein SH, Nachbagauer R, Craft J. CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response. Journal Of Experimental Medicine 2020, 218: e20200547. PMID: 33326020, PMCID: PMC7748821, DOI: 10.1084/jem.20200547.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAntigensB-LymphocytesCD4 AntigensDisease Models, AnimalEpitopesForkhead Transcription FactorsGerminal CenterHumansImmunityImmunologic MemoryInfluenza, HumanInfluenzavirus BIntegrasesMice, Inbred C57BLOrthomyxoviridae InfectionsReceptors, Antigen, B-CellSpecies SpecificityT-Lymphocytes, RegulatoryVaccinationConceptsB cell responsesGerminal center B cell responsesFollicular regulatory T cellsRegulatory T cellsTfr cellsCell responsesT cellsViral challengeHumoral memoryVirus-specific B cell responsesAntigen-specific B cell responsesFollicular helper T cellsHA stalk regionHelper T cellsInfluenza virus infectionGerminal center developmentAntibody responsePlasma cellsVirus infectionImmunization modelAntibody productionBCR repertoireInfluenza virusRepeated exposureInfluenza virus glycoproteinsSeasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults
Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, Belshe RB, Kaech SM, Shaw AC, Kleinstein SH. Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults. The Journal Of Immunology 2020, 204: 1661-1673. PMID: 32060136, PMCID: PMC7755271, DOI: 10.4049/jimmunol.1900922.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAgingAntibodies, ViralCohort StudiesFemaleGene Expression ProfilingHemagglutination Inhibition TestsHumansImmunogenicity, VaccineInfluenza A virusInfluenza VaccinesInfluenza, HumanMaleNK Cell Lectin-Like Receptor Subfamily BOligonucleotide Array Sequence AnalysisSeasonsTranscriptomeVaccinationVaccines, InactivatedYoung AdultConceptsVaccine-induced Ab responsesOlder adultsInfluenza vaccinationDays postvaccinationInfluenza vaccineAb responsesMore effective influenza vaccinesImportant public health toolInactivated influenza vaccinationSeasonal influenza vaccineVaccine-induced immunityEffective influenza vaccinesMolecular signaturesEffects of immunosenescencePublic health toolImmune signaturesVaccination seasonVaccine responsesVaccine compositionSubset of individualsAge groupsHealth toolsSingle age groupAdultsPostvaccination
2019
Repertoire-wide phylogenetic models of B cell molecular evolution reveal evolutionary signatures of aging and vaccination
Hoehn KB, Vander Heiden JA, Zhou JQ, Lunter G, Pybus OG, Kleinstein SH. Repertoire-wide phylogenetic models of B cell molecular evolution reveal evolutionary signatures of aging and vaccination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22664-22672. PMID: 31636219, PMCID: PMC6842591, DOI: 10.1073/pnas.1906020116.Peer-Reviewed Original ResearchGene set meta-analysis with Quantitative Set Analysis for Gene Expression (QuSAGE)
Meng H, Yaari G, Bolen CR, Avey S, Kleinstein SH. Gene set meta-analysis with Quantitative Set Analysis for Gene Expression (QuSAGE). PLOS Computational Biology 2019, 15: e1006899. PMID: 30939133, PMCID: PMC6461294, DOI: 10.1371/journal.pcbi.1006899.Peer-Reviewed Original Research
2017
Multiple network-constrained regressions expand insights into influenza vaccination responses
Avey S, Mohanty S, Wilson J, Zapata H, Joshi SR, Siconolfi B, Tsang S, Shaw AC, Kleinstein SH. Multiple network-constrained regressions expand insights into influenza vaccination responses. Bioinformatics 2017, 33: i208-i216. PMID: 28881994, PMCID: PMC5870750, DOI: 10.1093/bioinformatics/btx260.Peer-Reviewed Original Research
2015
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, Siconolfi B, Park K, Gill TM, Belshe RB, Kaech SM, Shadel GS, Kleinstein SH, Shaw AC. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. Aging 2015, 7: 38-51. PMID: 25596819, PMCID: PMC4356402, DOI: 10.18632/aging.100720.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAgingCells, CulturedDNA, MitochondrialFemaleGene Expression ProfilingGene Expression RegulationGenome-Wide Association StudyHumansInfluenza VaccinesInfluenza, HumanLeukocytes, MononuclearMaleMitochondriaMitochondrial TurnoverOligonucleotide Array Sequence AnalysisOxidative PhosphorylationSeasonsTime FactorsTreatment OutcomeVaccinationYoung AdultConceptsPlasma cell signatureDay 2Influenza vaccinationDay 7Cell signatureOlder adultsInfluenza vaccine responsesAdults meeting criteriaType I interferon responseAge-associated impairmentAge-dependent alterationsI interferon responseMitochondrial biogenesisResponse signatureVaccine seasonVaccine respondersFrail subjectsInfluenza vaccineVaccine responsesVaccine responsivenessGene expression microarray analysisAbsent responseYounger respondersDay 28Meeting criteria
2014
Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults
Mohanty S, Joshi SR, Ueda I, Wilson J, Blevins TP, Siconolfi B, Meng H, Devine L, Raddassi K, Tsang S, Belshe RB, Hafler DA, Kaech SM, Kleinstein SH, Trentalange M, Allore HG, Shaw AC. Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults. The Journal Of Infectious Diseases 2014, 211: 1174-1184. PMID: 25367297, PMCID: PMC4366602, DOI: 10.1093/infdis/jiu573.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedCytokinesDual Specificity Phosphatase 1FemaleGene Expression RegulationGPI-Linked ProteinsHumansImmunity, InnateInfluenza VaccinesInfluenza, HumanInterleukin-10Interleukin-6Lipopolysaccharide ReceptorsMaleMonocytesPhosphorylationReceptors, IgGSignal TransductionSTAT3 Transcription FactorTumor Necrosis Factor-alphaVaccinationYoung AdultConceptsOlder adultsInfluenza vaccinationInflammatory monocytesInterleukin-10Cytokine productionOlder subjectsAnti-inflammatory cytokine interleukin-10Influenza vaccine antibody responseTumor necrosis factor αImpaired vaccine responsesVaccine antibody responseIL-10 productionCytokine interleukin-10Proinflammatory cytokine productionNecrosis factor αAge-associated elevationPhosphorylated signal transducerVaccine responsesAntibody responseInterleukin-6Immune responseMonocyte populationsDay 28Intracellular stainingVaccinationTLR4 Ligands Lipopolysaccharide and Monophosphoryl Lipid A Differentially Regulate Effector and Memory CD8+ T Cell Differentiation
Cui W, Joshi NS, Liu Y, Meng H, Kleinstein SH, Kaech SM. TLR4 Ligands Lipopolysaccharide and Monophosphoryl Lipid A Differentially Regulate Effector and Memory CD8+ T Cell Differentiation. The Journal Of Immunology 2014, 192: 4221-4232. PMID: 24659688, PMCID: PMC4071140, DOI: 10.4049/jimmunol.1302569.Peer-Reviewed Original ResearchConceptsT cell differentiationT cellsEffector cellsTLR ligandsToll/IL-1R domain-containing adapterClonal expansionMore memory T cellsMemory T cellsT cell memoryEffector cell expansionTLR4 ligand LPSMonophosphoryl lipid ARole of adjuvantsTLR4 ligand lipopolysaccharideCell differentiationGene expression signaturesMemory CD8LPS-TLR4TLR4 ligandMonophosphoryl lipidLigand LPSLigand lipopolysaccharideAb productionSecondary infectionCell memoryHigh-resolution antibody dynamics of vaccine-induced immune responses
Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Heiden J, Kelton W, Jung S, Liu Y, Laserson J, Chari R, Lee JH, Bachelet I, Hickey B, Lieberman-Aiden E, Hanczaruk B, Simen BB, Egholm M, Koller D, Georgiou G, Kleinstein SH, Church GM. High-resolution antibody dynamics of vaccine-induced immune responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4928-4933. PMID: 24639495, PMCID: PMC3977259, DOI: 10.1073/pnas.1323862111.Peer-Reviewed Original Research