2024
Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites
Lapidus S, Goheen M, Sy M, Deme A, Ndiaye I, Diedhiou Y, Mbaye A, Hagadorn K, Sene S, Pouye M, Thiam L, Ba A, Guerra N, Mbengue A, Raduwan H, Gagnon J, Vigan-Womas I, Parikh S, Ko A, Ndiaye D, Fikrig E, Chuang Y, Bei A. Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites. The Journal Of Infectious Diseases 2024, jiae525. PMID: 39475423, DOI: 10.1093/infdis/jiae525.Peer-Reviewed Original ResearchModerate transmission areasMosquito salivary proteinsModerately endemic areaAntibody responseMosquito exposureTransmission seasonP. falciparum infectionMalaria transmission seasonMalaria transmission intensityExposure to infectious mosquitoesMosquito bitesEntomological inoculation rateEndemic areasHuman immune responseInfected mosquito bitesTransmission areasDecline 3 monthsNo antibody responseExposure to infected mosquitoesP. falciparumControl cohortExposure to mosquitoesBead-based assayImmune responseSalivary proteins
2023
Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients
Diray-Arce J, Fourati S, Jayavelu N, Patel R, Maguire C, Chang A, Dandekar R, Qi J, Lee B, van Zalm P, Schroeder A, Chen E, Konstorum A, Brito A, Gygi J, Kho A, Chen J, Pawar S, Gonzalez-Reiche A, Hoch A, Milliren C, Overton J, Westendorf K, Network I, Abraham J, Adkisson M, Albert M, Torres L, Alvarenga B, Anderson M, Anderson E, Arnett A, Asashima H, Atkinson M, Baden L, Barton B, Beach K, Beagle E, Becker P, Bell M, Bernui M, Bime C, Kumar A, Booth L, Borresen B, Brakenridge S, Bristow L, Bryant R, Calfee C, Manuel J, Carrillo S, Chak S, Chang I, Connors J, Conway M, Corry D, Cowan D, Croen B, Dela Cruz C, Cusimano G, Eaker L, Edwards C, Ehrlich L, Elashoff D, Erickson H, Erle D, Farhadian S, Farrugia K, Fatou B, Fernandes A, Fernandez-Sesma A, Fragiadakis G, Furukawa S, Geltman J, Ghale R, Bermúdez M, Goonewardene M, Sanchez E, Guirgis F, Hafler D, Hamilton S, Harris P, Nemati A, Hendrickson C, Agudelo N, Hodder T, Holland S, Hough C, Huerta C, Hurley K, Hutton S, Iwasaki A, Jauregui A, Jha M, Johnson B, Joyner D, Kangelaris K, Kelly G, Khalil Z, Khan Z, Kheradmand F, Kim J, Kimura H, Ko A, Kohr B, Kraft M, Krummel M, Kutzler M, Lasky-Su J, Lee S, Lee D, Leipold M, Lentucci C, Leroux C, Lin E, Liu S, Love C, Lu Z, Maliskova L, Roth B, Manohar M, Martens M, McComsey G, McEnaney K, McLin R, Melamed E, Melnyk N, Mendez K, Messer W, Metcalf J, Michelotti G, Mick E, Mohanty S, Mosier J, Mulder L, Murphy M, Nadeau K, Nelson E, Nelson A, Nguyen V, Oberhaus J, Panganiban B, Pellegrini K, Pickering H, Powell D, Presnell S, Pulendran B, Rahman A, Sadeed A, Raskin A, Reed E, Pereira S, Rivera A, Rogers J, Rogers A, Rogowski B, Rooks R, Rosenberg-Hasson Y, Rothman J, Rousseau J, Salehi-Rad R, Saluvan M, Samaha H, Schaenman J, Schunk R, Semenza N, Sen S, Sevransky J, Seyfert-Margolis V, Shaheen T, Shaw A, Sieg S, Siegel S, Sigal N, Siles N, Simmons B, Simon V, Singh G, Sinko L, Smith C, Smolen K, Song L, Srivastava K, Sullivan P, Syphurs C, Tcheou J, Tegos G, Tharp G, Ally A, Tsitsiklis A, Ungaro R, Vaysman T, Viode A, Vita R, Wang X, Ward A, Ward D, Willmore A, Woloszczuk K, Wong K, Woodruff P, Xu L, van Haren S, van de Guchte A, Zhao Y, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, Grubaugh N, van Bakel H, Wilson M, Rajan J, Steen H, Eckalbar W, Cotsapas C, Langelier C, Levy O, Altman M, Maecker H, Montgomery R, Haddad E, Sekaly R, Esserman D, Ozonoff A, Becker P, Augustine A, Guan L, Peters B, Kleinstein S. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients. Cell Reports Medicine 2023, 4: 101079. PMID: 37327781, PMCID: PMC10203880, DOI: 10.1016/j.xcrm.2023.101079.Peer-Reviewed Original ResearchConceptsDisease courseFatal COVID-19 diseaseHospitalized COVID-19 patientsSevere disease courseCOVID-19 participantsCOVID-19 patientsTrajectory groupsHost immune responseCOVID-19 diseaseImmune correlatesAcute infectionClinical courseHospital admissionClinical outcomesFatal outcomeClinical prognosisImmune responseSevere diseaseLongitudinal bloodNasal samplesBiologic stateLongitudinal studyDistinct assaysCohortMolecular signatures
2022
Biannual and Quarterly Comparison Analysis of Agglutinating Antibody Kinetics on a Subcohort of Individuals Exposed to Leptospira interrogans in Salvador, Brazil
Cruz J, Nery N, Sacramento G, Victoriano R, Montenegro A, Santana J, Costa F, Ko A, Reis M, Wunder E. Biannual and Quarterly Comparison Analysis of Agglutinating Antibody Kinetics on a Subcohort of Individuals Exposed to Leptospira interrogans in Salvador, Brazil. Frontiers In Medicine 2022, 9: 862378. PMID: 35492362, PMCID: PMC9048256, DOI: 10.3389/fmed.2022.862378.Peer-Reviewed Original ResearchMicroscopic agglutination testAntibody kineticsEndemic areasReinfection eventsSubcohort of individualsBurden of leptospirosisLife-threatening diseaseProspective cohortClinical manifestationsAsymptomatic infectionHumoral responseRisk factorsImmune responseLeptospirosis infectionAgglutination testPaucity of informationSerological surveyLeptospirosisSample collection timeInfectionLeptospira interrogansSubcohortFurther studiesHigh rateDiseaseSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
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 proteomeKynurenic 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 malePatientsMalesOutcomesResponseMetabolitesDivergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.Peer-Reviewed Original ResearchNeurological symptomsImmune responseCerebrospinal fluidAnti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodiesCOVID-19Self-reactive immune responsesSARS-CoV-2 antibodiesCompartmentalized immune responseCSF immunoglobulin GRole of autoimmunityCOVID-19 patientsB cell responsesCoronavirus disease 2019Immune surveyNeurologic sequelaePulmonary infectionBrain infectionSerum antibodiesDisease 2019Monoclonal antibody targetsAnimal modelsTarget epitopesCell activationCell responsesSingle-cell RNA sequencingA live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus
Wunder EA, Adhikarla H, Hamond C, Bonner K, Liang L, Rodrigues CB, Bisht V, Nally JE, Alt DP, Reis MG, Diggle PJ, Felgner PL, Ko A. A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus. ELife 2021, 10: e64166. PMID: 33496263, PMCID: PMC7837694, DOI: 10.7554/elife.64166.Peer-Reviewed Original ResearchConceptsCross-protective immunityPathogenic Leptospira speciesTerms of morbidityLeptospira speciesTransient bacteremiaSingle doseAntibody responseImmune responseApplicable vaccinesVaccine candidatesAnimal modelsEffective preventionAttenuated mutantsZoonotic diseaseLeptospira genusPotential correlatesDisease transmissionDiseaseLeptospirosisImmunityBacteremiaMorbidityImmunizationVaccineRelevant proteins
2020
Sex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.Peer-Reviewed Original ResearchConceptsInnate immune cytokinesFemale patientsMale patientsImmune cytokinesDisease outcomeImmune responseCOVID-19COVID-19 disease outcomesPoor T cell responsesSARS-CoV-2 infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusSex-based approachModerate COVID-19Sex differencesRobust T cell activationT cell responsesWorse disease progressionWorse disease outcomesHigher plasma levelsNon-classical monocytesCoronavirus disease 2019T cell activationImmunomodulatory medicationsPlasma cytokinesEscape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella
Holzapfel M, Bonhomme D, Cagliero J, Vernel-Pauillac F, d’Andon M, Bortolussi S, Fiette L, Goarant C, Wunder EA, Picardeau M, Ko AI, Werling D, Matsui M, Boneca IG, Werts C. Escape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella. Frontiers In Immunology 2020, 11: 2007. PMID: 32849665, PMCID: PMC7431986, DOI: 10.3389/fimmu.2020.02007.Peer-Reviewed Original ResearchConceptsTLR5 recognitionHuman Toll-like receptorsTLR5-deficient miceToll-like receptorsInnate immune recognitionNOD-like receptorsBacterial cell wall componentsHeat-killed bacteriaInflammatory roleDeficient miceTLR5 activationImmune responseLive leptospiresTLR5Immune recognitionLive strainsStealth pathogenWorldwide zoonosisHost defenseBovine TLR5TLR5 activityLeptospira sppInfectionLeptospiresCentral localization
2016
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis
Lindow JC, Wunder EA, Popper SJ, Min JN, Mannam P, Srivastava A, Yao Y, Hacker KP, Raddassi K, Lee PJ, Montgomery RR, Shaw AC, Hagan JE, Araújo GC, Nery N, Relman DA, Kim CC, Reis MG, Ko AI. Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLOS Pathogens 2016, 12: e1005943. PMID: 27812211, PMCID: PMC5094754, DOI: 10.1371/journal.ppat.1005943.Peer-Reviewed Original ResearchConceptsHost immune responseHigh bacterial loadBacterial loadAcute leptospirosisCase fatalityFatal casesDisease progressionImmune responseHigher systemic bacterial loadsValuable new therapeutic approachPro-inflammatory cytokine receptorsAdaptive immune signaturesSystemic bacterial loadsIndependent risk factorTime of hospitalizationDuration of illnessHigh case fatalityPoor clinical outcomeNew therapeutic approachesBlood transcriptional profilingLimited study sizeFatal leptospirosisLethal leptospirosisRANTES levelsSerum cathelicidin
2001
Leptospiral Proteins Recognized during the Humoral Immune Response to Leptospirosis in Humans
Guerreiro H, Croda J, Flannery B, Mazel M, Matsunaga J, Reis M, Levett P, Ko A, Haake D. Leptospiral Proteins Recognized during the Humoral Immune Response to Leptospirosis in Humans. Infection And Immunity 2001, 69: 4958-4968. PMID: 11447174, PMCID: PMC98588, DOI: 10.1128/iai.69.8.4958-4968.2001.Peer-Reviewed Original ResearchConceptsHumoral immune responseImmune responseNatural infectionLeptospiral proteinsInfection-associated antigenConvalescent-phase seraPositive reactionConvalescent phaseHumoral responseHealthy individualsHuman leptospirosisControl individualsVaccine designImmunodominant antigensQuantitative immunoblot analysisTwo-dimensional immunoblotsProtein antigensPathogenic leptospiral strainsGenus LeptospiraInfectionAntigenLeptospirosisSerumImmunodominant proteinsPatients