2023
Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis
Barmada A, Klein J, Ramaswamy A, Brodsky N, Jaycox J, Sheikha H, Jones K, Habet V, Campbell M, Sumida T, Kontorovich A, Bogunovic D, Oliveira C, Steele J, Hall E, Pena-Hernandez M, Monteiro V, Lucas C, Ring A, Omer S, Iwasaki A, Yildirim I, Lucas C. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Science Immunology 2023, 8: eadh3455-eadh3455. PMID: 37146127, PMCID: PMC10468758, DOI: 10.1126/sciimmunol.adh3455.Peer-Reviewed Original ResearchConceptsMRNA vaccinesSARS-CoV-2 mRNA vaccinesSARS-CoV-2 mRNA vaccinationC-reactive protein levelsB-type natriuretic peptidePeripheral blood mononuclear cellsCardiac tissue inflammationDeep immune profilingSerum soluble CD163Vaccine-associated myocarditisCohort of patientsBlood mononuclear cellsCytotoxic T cellsLate gadolinium enhancementHypersensitivity myocarditisElevated troponinMRNA vaccinationImaging abnormalitiesNK cellsImmune profilingKiller cellsMyeloid responseNatriuretic peptideHumoral mechanismsInflammatory cytokinesEnhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
Moriyama M, Lucas C, Monteiro V, Initiative Y, Iwasaki A, Chen N, Breban M, Hahn A, Pham K, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Vogels C, Grubaugh N. Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221652120. PMID: 37036977, PMCID: PMC10120007, DOI: 10.1073/pnas.2221652120.Peer-Reviewed Original ResearchConceptsMHC-I expressionBreakthrough infectionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variantsMajor histocompatibility complex class I expressionCell-mediated immunityInfluenza virus infectionSARS-CoV-2 VOCsMHC-I upregulationClass I expressionSARS-CoV-2T cell recognitionVirus infectionMHC II expressionSpike proteinEnhanced inhibitionInfectionCell recognitionCommon mutationsReinfectionE proteinAntibodiesViral genesSubvariantsExpressionNonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging Variants
Petrone M, Lucas C, Menasche B, Breban M, Yildirim I, Campbell M, Omer S, Holmes E, Ko A, Grubaugh N, Iwasaki A, Wilen C, Vogels C, Fauver J. Nonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging Variants. Genome Biology And Evolution 2023, 15: evad052. PMID: 36974986, PMCID: PMC10113931, DOI: 10.1093/gbe/evad052.Peer-Reviewed Original ResearchSARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity
Jaycox J, Lucas C, Yildirim I, Dai Y, Wang E, Monteiro V, Lord S, Carlin J, Kita M, Buckner J, Ma S, Campbell M, Ko A, Omer S, Lucas C, Speake C, Iwasaki A, Ring A. SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity. Nature Communications 2023, 14: 1299. PMID: 36894554, PMCID: PMC9996559, DOI: 10.1038/s41467-023-36686-8.Peer-Reviewed Original ResearchConceptsVaccine-associated myocarditisAutoimmune patientsAutoantibody reactivitySARS-CoV-2 mRNA vaccinationVaccine-related adverse effectsSARS-CoV-2 immunitySARS-CoV-2 infectionAcute COVID-19Development of autoantibodiesCOVID-19 patientsAnti-viral immunityVirus-specific antibodiesCOVID-19 vaccineCOVID-19Humoral autoimmunityMRNA vaccinationAutoantibody responsePost vaccinationAutoantibody developmentAutoimmune diseasesHumoral responseHealthy individualsPatientsAntigen profilingAdverse effectsPolyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens
Fang Z, Monteiro V, Renauer P, Shang X, Suzuki K, Ling X, Bai M, Xiang Y, Levchenko A, Booth C, Lucas C, Chen S. Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens. Cell Research 2023, 33: 407-410. PMID: 36879038, PMCID: PMC9988199, DOI: 10.1038/s41422-023-00792-5.Peer-Reviewed Original ResearchPD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2022
Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5
Fang Z, Monteiro VS, Hahn AM, Grubaugh ND, Lucas C, Chen S. Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5. Cell Discovery 2022, 8: 108. PMID: 36220819, PMCID: PMC9552143, DOI: 10.1038/s41421-022-00473-4.Peer-Reviewed Original ResearchDistinguishing features of Long COVID identified through immune profiling.
Klein J, Wood J, Jaycox J, Lu P, Dhodapkar RM, Gehlhausen JR, Tabachnikova A, Tabacof L, Malik AA, Kamath K, Greene K, Monteiro VS, Peña-Hernandez M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Silva J, Mccarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng TJ, Xu L, Yildirim I, Krumholz HM, Shon J, Medzhitov R, Omer SB, van Dijk D, Ring AM, Putrino D, Iwasaki A. Distinguishing features of Long COVID identified through immune profiling. MedRxiv 2022 PMID: 35982667, DOI: 10.1101/2022.08.09.22278592.Peer-Reviewed Original ResearchHeterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
Fang Z, Peng L, Lucas C, Lin Q, Zhou L, Yang L, Feng Y, Ren P, Renauer PA, Monteiro VS, Hahn AM, Park JJ, Zhou X, Grubaugh N, Wilen C, Chen S. Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2. Cell Discovery 2022, 8: 69. PMID: 35853867, PMCID: PMC9295082, DOI: 10.1038/s41421-022-00435-w.Peer-Reviewed Original ResearchNo evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
Lu-Culligan A, Tabachnikova A, Pérez-Then E, Tokuyama M, Lee HJ, Lucas C, Monteiro V, Miric M, Brache V, Cochon L, Muenker MC, Mohanty S, Huang J, Kang I, Dela Cruz C, Farhadian S, Campbell M, Yildirim I, Shaw AC, Ma S, Vermund SH, Ko AI, Omer SB, Iwasaki A. No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination. PLOS Biology 2022, 20: e3001506. PMID: 35609110, PMCID: PMC9129011, DOI: 10.1371/journal.pbio.3001506.Peer-Reviewed Original ResearchConceptsCOVID-19 mRNA vaccinationMRNA vaccinationEarly pregnancyFetal sizeCoronavirus disease 2019 (COVID-19) mRNA vaccinationSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Maternal antibody statusAdverse neonatal outcomesSyndrome coronavirus 2Birth defectsPolyinosinic-polycytidylic acidCrown-rump lengthGross birth defectsUnvaccinated adultsMaternal illnessNeonatal outcomesVaccinated adultsAntibody statusTLR3 agonistEarly immunizationMurine pregnancyAntibody inductionCoronavirus 2Multiscale PHATE identifies multimodal signatures of COVID-19
Kuchroo M, Huang J, Wong P, Grenier JC, Shung D, Tong A, Lucas C, Klein J, Burkhardt DB, Gigante S, Godavarthi A, Rieck B, Israelow B, Simonov M, Mao T, Oh JE, Silva J, Takahashi T, Odio CD, Casanovas-Massana A, Fournier J, Farhadian S, Dela Cruz C, Ko A, Hirn M, Wilson F, Hussin J, Wolf G, Iwasaki A, Krishnaswamy S. Multiscale PHATE identifies multimodal signatures of COVID-19. Nature Biotechnology 2022, 40: 681-691. PMID: 35228707, PMCID: PMC10015653, DOI: 10.1038/s41587-021-01186-x.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingTransposase-accessible chromatinSingle-cell sequencingRNA sequencingBiological insightsPopulation groupingsSophisticated computational toolsBiological featuresSequencingFlow cytometryComputational toolsChromatinBiomedical communityDifferent data typesCell responsesCellsPhateDevelopment and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses
Wisnewski AV, Liu J, Lucas C, Klein J, Iwasaki A, Cantley L, Fazen L, Luna J, Slade M, Redlich CA. Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses. PLOS ONE 2022, 17: e0262657. PMID: 35041700, PMCID: PMC8765639, DOI: 10.1371/journal.pone.0262657.Peer-Reviewed Original ResearchConceptsPlaque reduction neutralization testCOVID-19 patientsVaccine responsesRecovered COVID-19 patientsSARS-CoV-2 immunityBooster vaccine dosesMRNA vaccine responsePost-vaccine seraCompetitive ELISAEnzyme 2 (ACE2) receptorReduction neutralization testType of vaccineSARS-CoV-2 spike protein receptorSpike protein receptorVaccine seraVaccine recipientsPost vaccinationVaccinated individualsVaccine dosesViral culturePrior historyViral neutralizationNeutralization testBooster shotsPost vaccine
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 efficacyImpact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Lucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw A, Ko A, Omer S, Grubaugh N, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, PMCID: PMC9348899, DOI: 10.1038/s41586-021-04085-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 variantsMRNA vaccine-induced immunityT-cell activation markersSARS-CoV-2 antibodiesSecond vaccine doseVaccine-induced immunityCell activation markersT cell responsesHigh antibody titresSARS-CoV-2Vaccine boosterVaccine doseActivation markersVaccine dosesHumoral immunityAntibody titresMRNA vaccinesVitro stimulationNeutralization capacityNeutralization responseCell responsesE484KNucleocapsid peptideAntibody-binding sitesGreater reductionAssociations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel
Zell J, Wisnewski AV, Liu J, Klein J, Lucas C, Slade M, Iwasaki A, Redlich CA. Associations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel. PLOS ONE 2021, 16: e0251114. PMID: 34460832, PMCID: PMC8405017, DOI: 10.1371/journal.pone.0251114.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Live SARS-CoV-2Moderate SARS-CoV-2SARS-CoV-2 seroprevalenceWork-related risk factorsTransportation-related occupationsSerum IgG levelsAntigen-specific IgGIgG seropositivity rateBiomarkers of infectionSARS-CoV-2 spikeCOVID-19 exposureUS National Guard soldiersMilitary personnelIgG levelsSeropositivity rateHumoral responseSerum IgGViral exposureBlack raceRisk factorsOdds ratioStudy populationNational Guard soldiersDemographic dataKynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolitesLongitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient.
Klein J, Brito A, Trubin P, Lu P, Wong P, Alpert T, Pena-Hernandez M, Haynes W, Kamath K, Liu F, Vogels C, Fauver J, Lucas C, Oh JE, Mao T, Silva J, Wyllie A, Muenker MC, Casanovas-Massana A, Moore A, Petrone M, Kalinich C, Cruz CD, Farhadian S, Ring A, Shon J, Ko A, Grubaugh N, Goldman-Israelow B, Iwasaki A, Azar M. Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient. Research Square 2021 PMID: 34013255, PMCID: PMC8132249, DOI: 10.21203/rs.3.rs-405958/v1.Peer-Reviewed Original Research
2018
Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection
Lucas CGO, Kitoko JZ, Ferreira FM, Suzart VG, Papa MP, Coelho SVA, Cavazzoni CB, Paula-Neto HA, Olsen PC, Iwasaki A, Pereira RM, Pimentel-Coelho PM, Vale AM, de Arruda LB, Bozza MT. Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection. Nature Communications 2018, 9: 3136. PMID: 30087337, PMCID: PMC6081430, DOI: 10.1038/s41467-018-05519-4.Peer-Reviewed Original ResearchConceptsT cellsZika virusMurine adoptive transfer modelParticipation of CD4Adoptive transfer modelT cell responsesImportance of CD4Protective adaptive immunityRapid disease onsetZika virus infectionFuture vaccine designAntibody-mediated resistanceCytotoxic CD8Viral loadZIKV infectionAntibody responsePrimary infectionRecipient miceDisease onsetVirus infectionProtective effectAdaptive immunityIFNγ signalingCD4B lymphocytes
2016
Dendritic cells primed with a chimeric plasmid containing HIV‐1‐gag associated with lysosomal‐associated protein‐1 (LAMP/gag) is a potential therapeutic vaccine against HIV
Lucas C, Matassoli F, Peçanha L, Santillo B, da Silva Oliveira L, Oshiro T, Marques E, Oxenius A, de Arruda L. Dendritic cells primed with a chimeric plasmid containing HIV‐1‐gag associated with lysosomal‐associated protein‐1 (LAMP/gag) is a potential therapeutic vaccine against HIV. The FASEB Journal 2016, 30: 2970-2984. PMID: 27199296, DOI: 10.1096/fj.201500059.Peer-Reviewed Original ResearchConceptsT cell responsesPotential therapeutic vaccineDendritic cellsTherapeutic vaccinesT cellsImmune responseHIV-specific cellular immune responsesGreater T cell responsesPotential of DCUpregulation of CD38Human dendritic cellsCellular immune responsesProtein 1Immunization of miceMouse dendritic cellsTNF-α productionHIV infectionAntibody levelsHLA-DRVaccine efficacyDNA vaccineT lymphocytesGranzyme BImmune functionVaccine vehicle
2015
Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus
Medaglia M, Moussatché N, Nitsche A, Dabrowski P, Li Y, Damon I, Lucas C, Arruda L, Damaso C. Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus. Journal Of Virology 2015, 89: 11909-11925. PMID: 26378174, PMCID: PMC4645304, DOI: 10.1128/jvi.01833-15.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBase SequenceBayes TheoremBiological EvolutionBrazilCell LineComet AssayEnzyme-Linked Immunosorbent AssayFemaleFluorescent Antibody TechniqueHumansImmunoglobulin GMiceMice, Inbred BALB CModels, GeneticMolecular Sequence DataPhylogenySequence Analysis, DNASmallpoxSpecies SpecificityVaccinia virusViral VaccinesVirulenceVirulence FactorsConceptsFirst-generation vaccinesSmallpox vaccineSecond-generation smallpox vaccineVaccine strainNew-generation smallpox vaccinesVaccinia virusProtective immune responseIntensive vaccination programsImmunological featuresInfected miceHealth care standardsImmune protectionVaccination programLethal infectionImmune responseVACV strainVaccineCare standardsSmallpox eradication programmeLow virulenceAdverse effectsVACVLow pathogenicitySmallpox eradicationVaccine producers