2021
Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine
Trentelman JJA, Tomás-Cortázar J, Knorr S, Barriales D, Hajdusek O, Sima R, Ersoz JI, Narasimhan S, Fikrig E, Nijhof AM, Anguita J, Hovius JW. Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine. Scientific Reports 2021, 11: 15745. PMID: 34344917, PMCID: PMC8333314, DOI: 10.1038/s41598-021-92538-9.Peer-Reviewed Original ResearchConceptsTick salivary gland proteinsLyme borreliosisVaccination studiesTick biteTick-borne encephalitis virusB. burgdorferi transmissionMultiple tick bitesYeast surface display libraryHuman infectious diseasesImmunization of rabbitsVaccination platformAnti-tick effectsAnti-tick vaccinesEncephalitis virusImmunodominant antigensInfectious diseasesNon-natural hostsTick immunityTick feedingImmunityBorreliosisBiteVaccineAntigenHuman serum
2015
Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut
Coumou J, Narasimhan S, Trentelman JJ, Wagemakers A, Koetsveld J, Ersoz JI, Oei A, Fikrig E, Hovius JW. Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut. Journal Of Molecular Medicine 2015, 94: 361-370. PMID: 26594018, PMCID: PMC4803822, DOI: 10.1007/s00109-015-1365-0.Peer-Reviewed Original ResearchConceptsB. burgdorferi transmissionTick gutLyme borreliosisTick feedingMurine modelVaccine targetsUninfected ticksRNA interferenceInfected ticksSalivary glandsBorrelia burgdorferiPotential targetGut tissueB. burgdorferiCausative agentIxodes ticksGutPrevious screeningTick proteinsGut cellsBurgdorferiMiceTicks resultsBorreliosisConfocal microscopy
2012
The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity
Silver AC, Arjona A, Walker WE, Fikrig E. The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity. Immunity 2012, 36: 251-261. PMID: 22342842, PMCID: PMC3315694, DOI: 10.1016/j.immuni.2011.12.017.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Receptor 9Adaptive immune responsesInnate immune systemCircadian molecular clockSepsis inductionTLR9 expressionTLR9 ligandsImmune responseVaccination modelAdaptive immunityMouse modelImmune systemDisease severityHomeostatic processesCircadian rhythmBiologic processesDirect molecular linkMolecular linkRhythmSepsisImmunotherapyImmunoprophylaxisExpressionInnate
2011
Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV‐1 envelope proteins are largely mediated via human CD5+ B cells
Biswas S, Chang H, Sarkis PT, Fikrig E, Zhu Q, Marasco WA. Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV‐1 envelope proteins are largely mediated via human CD5+ B cells. Immunology 2011, 134: 419-433. PMID: 22044090, PMCID: PMC3230796, DOI: 10.1111/j.1365-2567.2011.03501.x.Peer-Reviewed Original ResearchConceptsHumoral immune responseImmune responseBLT miceB cellsB lymphocytesVaccine-induced humoral immune responsesVaccine-induced immune responsesVaccine-induced antibody responsesNon-obese diabetic/T cell-independent pathwayHIV-1 envelope proteinSecondary immune responseSingle intramuscular immunizationSpecific IgM levelsViral envelope antigensB cell subsetsAntigen-specific human antibodiesFollicular B cellsCytokines/growth factorsEnvelope proteinHuman B lymphocytesHuman lymphoid systemMature follicular B cellsWest Nile virus envelope proteinHuman T lymphocytesIdentification and Characterization of Ixodes scapularis Antigens That Elicit Tick Immunity Using Yeast Surface Display
Schuijt TJ, Narasimhan S, Daffre S, DePonte K, Hovius JW, Veer C, van der Poll T, Bakhtiari K, Meijers JC, Boder ET, van Dam AP, Fikrig E. Identification and Characterization of Ixodes scapularis Antigens That Elicit Tick Immunity Using Yeast Surface Display. PLOS ONE 2011, 6: e15926. PMID: 21246036, PMCID: PMC3016337, DOI: 10.1371/journal.pone.0015926.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensImmunityImmunizationIxodesNymphPeptide LibraryRabbitsSalivary GlandsTicksYeastsConceptsSalivary antigensTick salivary antigensPotential vaccine candidatesAnti-coagulant activityTick biteImmunization studiesVaccine candidatesAnti-complement activityTick antigensRepeated exposureTick immunityAntigenRabbit serumHall markTicks resultsImmunitySerumYeast surface display libraryRabbitsDisplay libraryIxodes scapularisDrosophila expression systemP19Surface display libraryP8
2010
Tick Histamine Release Factor Is Critical for Ixodes scapularis Engorgement and Transmission of the Lyme Disease Agent
Dai J, Narasimhan S, Zhang L, Liu L, Wang P, Fikrig E. Tick Histamine Release Factor Is Critical for Ixodes scapularis Engorgement and Transmission of the Lyme Disease Agent. PLOS Pathogens 2010, 6: e1001205. PMID: 21124826, PMCID: PMC2991271, DOI: 10.1371/journal.ppat.1001205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorBlotting, WesternBorrelia burgdorferiFeeding BehaviorFemaleHistamineHumansImmunizationIxodesLyme DiseaseMiceMice, Inbred C3HReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSalivaTick InfestationsTumor Protein, Translationally-Controlled 1ConceptsTick-borne pathogensB. burgdorferi transmissionTick engorgementB. burgdorferi burdenHistamine-releasing factorRapid feeding phaseBurgdorferi-infected ticksAnimal healthTick feedingTick salivaDiverse infectious agentsDisease agentsTicksIxodes scapularisLyme disease agentRNA interferenceFeeding phaseVaccine potentialQuantitative reverse transcription PCRReverse transcription-PCRHistamine releaseEffective vaccineVascular permeabilityBlood flowInfectious agents
2001
Immunization of Mice Against West Nile Virus with Recombinant Envelope Protein
Wang T, Anderson J, Magnarelli L, Wong S, Koski R, Fikrig E. Immunization of Mice Against West Nile Virus with Recombinant Envelope Protein. The Journal Of Immunology 2001, 167: 5273-5277. PMID: 11673542, DOI: 10.4049/jimmunol.167.9.5273.Peer-Reviewed Original ResearchConceptsWN virus infectionRecombinant E proteinWest Nile virusVirus infectionC3H/HeN miceE proteinNile virusImmunization of miceRecombinant envelope proteinsPassive administrationCandidate vaccinesHeN miceFatal encephalitisImmunization experimentsImmunoblot assayWN virusInfectionVirus isolatesEnvelope proteinProtein antiserumVirusMiceEncephalitisPatientsImmunization
1997
Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells.
Fikrig E, Barthold SW, Chen M, Chang CH, Flavell RA. Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells. The Journal Of Immunology 1997, 159: 5682-6. PMID: 9548512, DOI: 10.4049/jimmunol.159.11.5682.Peer-Reviewed Original ResearchConceptsMHC class IIT cellsClass IINaive C3H/HeN miceC3H/HeN miceC57/BL6 miceCIITA-deficient miceRegression of arthritisResolution of arthritisResolution of carditisDevelopment of arthritisMurine Lyme borreliosisMHC class II transactivatorClass II moleculesClass II transactivatorIgG2b AbsProtective antibodiesBL6 miceHeN miceDeficient miceProtective AbsSCID micePersistent infectionArthritisCD4 repertoireTemporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host.
Das S, Barthold SW, Giles SS, Montgomery RR, Telford SR, Fikrig E. Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. Journal Of Clinical Investigation 1997, 99: 987-995. PMID: 9062357, PMCID: PMC507907, DOI: 10.1172/jci119264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupElectrophoresis, Gel, Pulsed-FieldEnzyme-Linked Immunosorbent AssayFemaleFlagellinFluorescent Antibody Technique, IndirectGene Expression Regulation, BacterialHumansImmunizationImmunization, PassiveImmunoblottingIxodesLipoproteinsLyme DiseaseMiceMice, Inbred C3HPlasmidsPolymerase Chain ReactionRecombinant ProteinsRNA, MessengerTime FactorsConceptsInfected miceHumoral responseLate-stage Lyme diseaseMarkers of infectionCourse of diseaseMurine Lyme borreliosisB. burgdorferiB. burgdorferi infectionHuman humoral responseIxodes dammini ticksBurgdorferi-infected miceLyme arthritisActive immunizationMammalian hostsPassive transferBurgdorferi infectionC3H miceMurine infectionDay 14P21 antibodyP21 expressionLyme borreliosisLyme diseaseMiceInfection
1995
Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi OspA or B.
Fikrig E, Tao H, Chen M, Barthold SW, Flavell RA. Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi OspA or B. Journal Of Clinical Investigation 1995, 96: 1706-1714. PMID: 7560061, PMCID: PMC185806, DOI: 10.1172/jci118215.Peer-Reviewed Original ResearchConceptsC3H/HeJTransgenic miceLyme borreliosisImmune responseB. burgdorferi-specific antibodyLyme diseaseMajor histocompatibility complex class IBurgdorferi-specific antibodiesRegression of arthritisCellular immune responsesDevelopment of arthritisHistocompatibility complex class IRole of immunityB. burgdorferi antigensComplex class ISurface protein ABorrelia burgdorferi outer surface protein AOuter surface protein ATolerant miceNontransgenic littermatesB6 miceSCID miceImmunodeficient miceB antibodiesC57BL/6 backgroundCircumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi
Barthold SW, Fikrig E, Bockenstedt LK, Persing DH. Circumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi. Infection And Immunity 1995, 63: 2255-2261. PMID: 7768606, PMCID: PMC173294, DOI: 10.1128/iai.63.6.2255-2261.1995.Peer-Reviewed Original ResearchConceptsInfectious doseInfected skinCultured Borrelia burgdorferiBorrelia burgdorferiLow-dose infectionMedian infectious doseNumber of spirochetesSurface protein ASyringe challengeB. burgdorferi OspAOuter surface protein AChallenge doseDisseminated infectionHost-adapted spirochetesSkin transplantsSyngenic miceOuter surface proteinsMiceHyperimmune serumDoseImmunologic recognitionInfectionSeroconversionTransplantationDisease developmentBorrelia burgdorferi genes selectively expressed in the infected host.
Suk K, Das S, Sun W, Jwang B, Barthold SW, Flavell RA, Fikrig E. Borrelia burgdorferi genes selectively expressed in the infected host. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 4269-4273. PMID: 7753795, PMCID: PMC41925, DOI: 10.1073/pnas.92.10.4269.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigen-Antibody ReactionsAntigens, BacterialBacterial VaccinesBase SequenceBlotting, NorthernBorrelia burgdorferi GroupDNA PrimersDNA, BacterialGene ExpressionGene Transfer TechniquesGenes, BacterialGenomic LibraryImmunizationMiceMice, Inbred C3HMolecular Sequence DataPolymerase Chain ReactionSequence Homology, Amino AcidConceptsInfected hostRNA PCRDifferential screeningScreening strategyExpression libraryB. burgdorferiSelective expressionNorthern blot analysisBlot analysisMiceBorrelia burgdorferi genesB. burgdorferi genesVivoGene transfer systemMicrobial genesScreening methodPathogenic microorganismsScreeningGenesAntigen
1994
Partial destruction of Borrelia burgdorferi within ticks that engorged on OspE- or OspF-immunized mice
Nguyen TP, Lam TT, Barthold SW, Telford SR, Flavell RA, Fikrig E. Partial destruction of Borrelia burgdorferi within ticks that engorged on OspE- or OspF-immunized mice. Infection And Immunity 1994, 62: 2079-2084. PMID: 8168973, PMCID: PMC186469, DOI: 10.1128/iai.62.5.2079-2084.1994.Peer-Reviewed Original ResearchConceptsEarly-stage disease patientsMajority of patientsLate-stage diseaseSerum of miceLyme disease vaccineB. burgdorferiB. burgdorferi organismsExamination of seraNumber of spirochetesOuter surface protein ESyringe challengeDisease patientsImmune responseDisease vaccinePatientsHigh titersLyme diseaseMiceAntibodiesDiseaseSerumBurgdorferiBorreliaDaysProtein E
1992
Roles of OspA, OspB, and flagellin in protective immunity to Lyme borreliosis in laboratory mice
Fikrig E, Barthold SW, Marcantonio N, Deponte K, Kantor FS, Flavell RA. Roles of OspA, OspB, and flagellin in protective immunity to Lyme borreliosis in laboratory mice. Infection And Immunity 1992, 60: 657-661. PMID: 1730500, PMCID: PMC257680, DOI: 10.1128/iai.60.2.657-661.1992.Peer-Reviewed Original ResearchConceptsProtective immunityProtective effectRecombinant outer surface protein AActive immunization experimentsSurface protein AOuter surface protein AB. burgdorferi proteinsActive immunizationResidual seraRecombinant OspAImmunization experimentsLyme borreliosisInfectionLyme disease agentMiceImmunityBorrelia burgdorferiAntibodiesImmunizationOspAOspBLaboratory miceSerumFlagellinDisease agents
1990
Protection of Mice Against the Lyme Disease Agent by Immunizing with Recombinant OspA
Fikrig E, Barthold S, Kantor F, Flavell R. Protection of Mice Against the Lyme Disease Agent by Immunizing with Recombinant OspA. Science 1990, 250: 553-556. PMID: 2237407, DOI: 10.1126/science.2237407.Peer-Reviewed Original ResearchConceptsRecombinant OspALyme borreliosisC3H/HeJ miceProtection of miceTick-borne illnessB. burgdorferi strain N40Recombinant OspA proteinSurface protein AOuter surface protein AHeJ miceLyme disease agentStrain N40Borrelia burgdorferiB. burgdorferiMiceOspABorreliosisOspA proteinBurgdorferiDisease agentsProtein AVaccineIllnessAntibodies