2023
Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans
Vylegzhanina A, Bespalov I, Novototskaya-Vlasova K, Hall B, Gleiberman A, Yu H, Leontieva O, Leonova K, Kurnasov O, Osterman A, Dy G, Komissarov A, Vasilieva E, Gehlhausen J, Iwasaki A, Ambrosone C, Tsuji T, Matsuzaki J, Odunsi K, Andrianova E, Gudkov A. Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans. Cancer Research Communications 2023, 3: 2256-2267. PMID: 37870410, PMCID: PMC10631453, DOI: 10.1158/2767-9764.crc-23-0289.Peer-Reviewed Original ResearchConceptsL1 antigenCancer typesDisease stage 1Discovery of autoantibodiesHigh IgG titersTumor-associated antigensDetermination of immunoreactivityTumor immunoreactivityCirculating AntibodiesIgG titersAntibody responseImmune responseLiver cancerReactive IgGHealthy individualsCurable cancer typesImmune systemAntigenNormal tissuesPatientsCancerEarly detectionElevated levelsCarcinogenic processAutoantibodiesDistinguishing features of long COVID identified through immune profiling
Klein J, Wood J, Jaycox J, Dhodapkar R, Lu P, Gehlhausen J, Tabachnikova A, Greene K, Tabacof L, Malik A, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott I, Valle G, Peña-Hernández M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng T, Xu L, Geraghty A, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick J, Kaminski N, Omer S, Krumholz H, Guan L, Dela Cruz C, van Dijk D, Ring A, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature 2023, 623: 139-148. PMID: 37748514, PMCID: PMC10620090, DOI: 10.1038/s41586-023-06651-y.Peer-Reviewed Original ResearchConceptsLong COVIDSARS-CoV-2Infection syndromeExaggerated humoral responseSoluble immune mediatorsEpstein-Barr virusPost-exertional malaiseCross-sectional studyHigher antibody responseImmune mediatorsImmune phenotypingImmune profilingHumoral responseAntibody responseLymphocyte populationsCOVID statusUnbiased machineCortisol levelsLC statusRelevant biomarkersViral pathogensSyndromeCOVIDFuture studiesBiological featuresAge-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose
Filardi B, Monteiro V, Schwartzmann P, do Prado Martins V, Zucca L, Baiocchi G, Malik A, Silva J, Hahn A, Chen N, Pham K, Pérez-Then E, Miric M, Brache V, Cochon L, Larocca R, Della Rosa Mendez R, Silveira D, Pinto A, Croda J, Yildirim I, Omer S, Ko A, Vermund S, Grubaugh N, Iwasaki A, Lucas C, Initiative Y, Vogels C, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W. Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose. Science Translational Medicine 2023, 15: eade6023. PMID: 36791210, DOI: 10.1126/scitranslmed.ade6023.Peer-Reviewed Original ResearchConceptsBooster doseAntibody responseNeutralization titersVirus-specific IgG titersOlder adultsAntiviral humoral immunityPlasma antibody responsesHigh-risk populationSARS-CoV-2 spikeYears of ageAge-dependent impairmentHeterologous regimensBooster dosesBooster vaccineCoronaVac vaccineIgG titersProtective immunityHumoral immunityHumoral responseCoronaVacOmicron waveBooster strategyAge groupsEarly controlVaccine
2022
Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration
Fiedler S, Devenish S, Morgunov A, Ilsley A, Ricci F, Emmenegger M, Kosmoliaptsis V, Theel E, Mills J, Sholukh A, Aguzzi A, Iwasaki A, Lynn A, Knowles T. Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration. Scientific Reports 2022, 12: 19791. PMID: 36396691, PMCID: PMC9672333, DOI: 10.1038/s41598-022-22214-z.Peer-Reviewed Original ResearchConceptsSerum antibody responseAntiviral activityHigh antiviral activityAntibody responseTherapeutic mAbsReduced antiviral activityVirus neutralization assaysSARS-CoV-2 virusSARS-CoV-2Convalescent individualsNeutralization assaysTherapeutic monoclonal antibodiesSame mAbMonoclonal antibodiesNew therapeuticsTherapeutic antibodiesMAbsAntibodiesRBDSotrovimabWild typeActivitySerumLack of association between pandemic chilblains and SARS-CoV-2 infection
Gehlhausen JR, Little AJ, Ko CJ, Emmenegger M, Lucas C, Wong P, Klein J, Lu P, Mao T, Jaycox J, Wang E, Ugwu N, Muenker C, Mekael D, Klein R, Patrignelli R, Antaya R, McNiff J, Damsky W, Kamath K, Shon J, Ring A, Yildirim I, Omer S, Ko A, Aguzzi A, Iwasaki A, Obaid A, Lu-Culligan A, Nelson A, Brito A, Nunez A, Martin A, Watkins A, Geng B, Kalinich C, Harden C, Todeasa C, Jensen C, Kim D, McDonald D, Shepard D, Courchaine E, White E, Song E, Silva E, Kudo E, DeIuliis G, Rahming H, Park H, Matos I, Nouws J, Valdez J, Fauver J, Lim J, Rose K, Anastasio K, Brower K, Glick L, Sharma L, Sewanan L, Knaggs L, Minasyan M, Batsu M, Petrone M, Kuang M, Nakahata M, Campbell M, Linehan M, Askenase M, Simonov M, Smolgovsky M, Sonnert N, Naushad N, Vijayakumar P, Martinello R, Datta R, Handoko R, Bermejo S, Prophet S, Bickerton S, Velazquez S, Alpert T, Rice T, Khoury-Hanold W, Peng X, Yang Y, Cao Y, Strong Y. Lack of association between pandemic chilblains and SARS-CoV-2 infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122090119. PMID: 35217624, PMCID: PMC8892496, DOI: 10.1073/pnas.2122090119.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionPrior SARS-CoV-2 infectionSARS-CoV-2PC biopsiesAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicT-cell receptor sequencingCell receptor sequencingT cell responsesCoronavirus 2 pandemicEnzyme-linked immunosorbent assayLack of associationCOVID toesSkin eruptionAntibody responseImmunohistochemistry studiesBackground seroprevalenceTissue microarrayViral infectionStimulation assaysCell responsesInfectionChilblainsImmunosorbent assayAbortive infection
2021
High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19
Haynes WA, Kamath K, Bozekowski J, Baum-Jones E, Campbell M, Casanovas-Massana A, Daugherty PS, Dela Cruz CS, Dhal A, Farhadian SF, Fitzgibbons L, Fournier J, Jhatro M, Jordan G, Klein J, Lucas C, Kessler D, Luchsinger LL, Martinez B, Catherine Muenker M, Pischel L, Reifert J, Sawyer JR, Waitz R, Wunder EA, Zhang M, Iwasaki A, Ko A, Shon J. High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19. Communications Biology 2021, 4: 1317. PMID: 34811480, PMCID: PMC8608966, DOI: 10.1038/s42003-021-02835-2.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 antibodiesRespiratory syndrome coronavirus 2SARS-CoV-2 epitopesSyndrome coronavirus 2SARS-CoV-2 strainsHigh-resolution epitope mappingCOVID-19SARS-CoV-2SARS-CoV-2 mutantsCoronavirus 2Antibody responseEffective vaccineImmune responseNeutralization activitySevere diseaseLarge cohortEpitope regionsAntibody epitopesEpitope mappingRelated coronavirusesTherapyVaccineViral proteomeAdaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Israelow B, Mao T, Klein J, Song E, Menasche B, Omer SB, Iwasaki A. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Science Immunology 2021, 6: eabl4509. PMID: 34623900, PMCID: PMC9047536, DOI: 10.1126/sciimmunol.abl4509.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Viral clearanceImmune determinantsMouse modelSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Cellular adaptive immunitySyndrome coronavirus 2Vivo protective capacityVariants of concernMRNA vaccinationHomologous infectionCellular immunityConvalescent miceCoronavirus 2Antibody responsePrimary infectionEffective vaccineAdaptive immunityConfer protectionInfectionNatural infectionProtective capacityClearanceDelayed production of neutralizing antibodies correlates with fatal COVID-19
Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie A, Campbell M, Lee A, Chun H, Grubaugh N, Schulz W, Farhadian S, Dela Cruz C, Ring A, Shaw A, Wisnewski A, Yildirim I, Ko A, Omer S, Iwasaki A. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1178-1186. PMID: 33953384, PMCID: PMC8785364, DOI: 10.1038/s41591-021-01355-0.Peer-Reviewed Original ResearchConceptsDeceased patientsAntibody levelsAntibody responseDisease severityAnti-S IgG levelsCOVID-19 disease outcomesFatal COVID-19Impaired viral controlWorse clinical progressionWorse disease severitySevere COVID-19Length of hospitalizationImmunoglobulin G levelsHumoral immune responseCoronavirus disease 2019COVID-19 mortalityCOVID-19Domain (RBD) IgGSeroconversion kineticsDisease courseIgG levelsClinical parametersClinical progressionHumoral responseDisease onset
2020
SARS-CoV-2 infection of the placenta
Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, Yasumoto Y, Vogels C, Casanovas-Massana A, Vijayakumar P, Geng B, Odio CD, Fournier J, Brito AF, Fauver JR, Liu F, Alpert T, Tal R, Szigeti-Buck K, Perincheri S, Larsen C, Gariepy AM, Aguilar G, Fardelmann KL, Harigopal M, Taylor HS, Pettker CM, Wyllie AL, Dela Cruz CS, Ring AM, Grubaugh ND, Ko AI, Horvath TL, Iwasaki A, Reddy UM, Lipkind HS. SARS-CoV-2 infection of the placenta. Journal Of Clinical Investigation 2020, 130: 4947-4953. PMID: 32573498, PMCID: PMC7456249, DOI: 10.1172/jci139569.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAbortion, TherapeuticAbruptio PlacentaeAdultBetacoronavirusCoronavirus InfectionsCOVID-19FemaleHumansMicroscopy, Electron, TransmissionPandemicsPhylogenyPlacentaPneumonia, ViralPre-EclampsiaPregnancyPregnancy Complications, InfectiousPregnancy Trimester, SecondRNA, ViralSARS-CoV-2Viral LoadConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 invasionMaternal antibody responseSymptomatic COVID-19Second trimester pregnancySyndrome coronavirus 2Coronavirus disease 2019Materno-fetal interfaceDense macrophage infiltratesPlacental abruptionSevere preeclampsiaMacrophage infiltratesSevere morbidityTrimester pregnancyPregnant womenCoronavirus 2Antibody responseBackgroundThe effectsDisease 2019Histological examinationImmunohistochemical assaysPlacentaThe potential danger of suboptimal antibody responses in COVID-19
Iwasaki A, Yang Y. The potential danger of suboptimal antibody responses in COVID-19. Nature Reviews Immunology 2020, 20: 339-341. PMID: 32317716, PMCID: PMC7187142, DOI: 10.1038/s41577-020-0321-6.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
Type 1 Interferon Regulates Inflammation Associated RBC Alloimmunization By Promoting Monocyte-Derived Dendritic Cell Erythrophagocytosis in Mice
Gibb D, Natarajan P, Liu J, Santhanakrishnan M, Iwasaki A, Hendrickson J. Type 1 Interferon Regulates Inflammation Associated RBC Alloimmunization By Promoting Monocyte-Derived Dendritic Cell Erythrophagocytosis in Mice. Blood 2016, 128: 19. DOI: 10.1182/blood.v128.22.19.19.Peer-Reviewed Original ResearchMonocyte-derived dendritic cellsReactivity of seraPeak antibody responseWT miceIfnar1-/- miceType 1 interferonDendritic cellsRBC transfusionPeripheral bloodAntibody responseRBC alloimmunizationAlloimmune responseSpecific IgGIgG antibodiesInflammatory diseasesMouse modelRBC antigensIndividual miceCCR2-/- miceFrequency of alloimmunizationHuman KEL glycoproteinFlow cytometric crossmatchActivation marker expressionDendritic cell activationRole of inflammationCD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens
Kumamoto Y, Hirai T, Wong PW, Kaplan DH, Iwasaki A. CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens. ELife 2016, 5: e17979. PMID: 27657168, PMCID: PMC5033605, DOI: 10.7554/elife.17979.Peer-Reviewed Original ResearchDendritic cellsAntibody responsePD-L1Protein antigensBlocking PD-1Follicular helper cellsPD-1 ligandsStrong antibody responseWild-type miceGerminal center B cellsTfh cellsPD-1Cell primingIgG responsesHelper cellsPD-L2Autoantibody generationSuccessful vaccineCD301bB cellsTransient depletionAntigenMiceAntibodiesNovel regulatory mechanism
2011
Microbiota regulates immune defense against respiratory tract influenza A virus infection
Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 5354-5359. PMID: 21402903, PMCID: PMC3069176, DOI: 10.1073/pnas.1019378108.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionVirus infectionDendritic cellsImmune responseCommensal bacteriaRespiratory influenza virus infectionToll-like receptor ligandsVirus-specific CD4CD8 T cellsT cell primingCommensal microbiota compositionProductive immune responseExpression of mRNADistal injectionLymph nodesImmune impairmentIntact microbiotaIL-1βAntibody responseImmune homeostasisRespiratory mucosaAntibiotic treatmentT cellsInflammasome activationCommensal microbiota
1999
Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization
Iwasaki A, Dela Cruz C, Young A, Barber B. Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization. Vaccine 1999, 17: 2081-2088. PMID: 10217610, DOI: 10.1016/s0264-410x(98)00411-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralAntigen PresentationBiolisticsCytokinesEpitopes, T-LymphocyteFemaleGenes, ViralHistocompatibility Antigens Class IInjections, IntramuscularMiceMice, Inbred StrainsNucleocapsid ProteinsNucleoproteinsOrthomyxoviridaeOrthomyxoviridae InfectionsPeptide FragmentsPlasmidsProtein Sorting SignalsRecombinant ProteinsRNA-Binding ProteinsT-Lymphocytes, CytotoxicTumor Cells, CulturedVaccines, DNAViral Core ProteinsConceptsCTL responsesCytotoxic T lymphocyte inductionEpitope-specific CTL responsesT lymphocyte responsesT lymphocyte inductionPlasmid DNA vaccineFull-length antigenLymphocyte responsesIL-12Lymphocyte inductionAntibody responseDNA immunizationDNA vaccineGene gun bombardmentPotent antibodiesGM-CSFCytokine combinationsNeedle injectionInfluenza virusSkeletal muscleSkin epidermisNucleoproteinMinimal effectResponseImmunization