2024
Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches
Johnson E, Hart T, Fikrig E. Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches. The Journal Of Infectious Diseases 2024, 230: s82-s86. PMID: 39140718, PMCID: PMC11322886, DOI: 10.1093/infdis/jiae202.Peer-Reviewed Original ResearchConceptsTransmission of tick-borne pathogensTick-borne pathogensIxodes spp ticksInhibited tick feedingTick feedingDisease vaccineTick vectorWildlife reservoirsOuter surface protein ALyme disease vaccineLyme diseaseTicksBorrelia burgdorferiLyme disease casesPreventing Lyme diseasePathogensFood and Drug AdministrationSurface protein AOspA-based vaccinesVaccineFeedingLymeProtein AFoodPrevent transmission
2023
Development of an mRNA-lipid nanoparticle vaccine against Lyme disease
Pine M, Arora G, Hart T, Bettini E, Gaudette B, Muramatsu H, Tombácz I, Kambayashi T, Tam Y, Brisson D, Allman D, Locci M, Weissman D, Fikrig E, Pardi N. Development of an mRNA-lipid nanoparticle vaccine against Lyme disease. Molecular Therapy 2023, 31: 2702-2714. PMID: 37533256, PMCID: PMC10492027, DOI: 10.1016/j.ymthe.2023.07.022.Peer-Reviewed Original ResearchConceptsLyme diseaseImmune responseCell-mediated immune responsesLyme disease vaccinePotent immune responsesProtein subunit vaccinesSARS-CoV-2Surface protein AVector-borne infectious diseasesMRNA-LNP vaccineOuter surface protein ASingle immunizationProtective efficacyMRNA vaccinesClinical vaccinesDisease vaccineNanoparticle vaccineSubunit vaccineVaccine developmentVaccineBacterial infectionsMRNA-LNPInfectious diseasesDiseaseMRNA platform
2004
TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi
Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, deSilva AM, Bao F, Yang X, Pypaert M, Pradhan D, Kantor FS, Telford S, Anderson JF, Fikrig E. TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi. Cell 2004, 119: 457-468. PMID: 15537536, DOI: 10.1016/j.cell.2004.10.027.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBase SequenceBorrelia burgdorferiCloning, MolecularGene Expression RegulationHost-Parasite InteractionsIntestinesIxodesLipoproteinsMiceMice, Inbred C3HMolecular Sequence DataReceptors, Cell SurfaceRecombinant ProteinsConceptsLyme disease agent Borrelia burgdorferiSurvival of spirochetesTick receptorMammalian hostsRNA interferenceEfficient colonizationTROSPAOuter surface protein ABorrelia burgdorferiPathogen adherencePathogen transmissionProtein AB. burgdorferi outer surface protein AMRNA levelsIxodes scapularisB. burgdorferiColonizationSurface protein AReceptorsArthropodsBurgdorferiMammalsRepressionSpirochetesTicks
2001
Inhibition of Borrelia burgdorferi-Tick Interactions In Vivo by Outer Surface Protein A Antibody
Pal U, Montgomery R, Lusitani D, Voet P, Weynants V, Malawista S, Lobet Y, Fikrig E. Inhibition of Borrelia burgdorferi-Tick Interactions In Vivo by Outer Surface Protein A Antibody. The Journal Of Immunology 2001, 166: 7398-7403. PMID: 11390491, DOI: 10.4049/jimmunol.166.12.7398.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsAntibodies, BacterialAntibodies, MonoclonalAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBinding Sites, AntibodyBorrelia burgdorferi GroupDigestive SystemEpitopesFemaleImmune SeraInjections, IntraperitonealInjections, SubcutaneousIxodesLipoproteinsLyme DiseaseLyme Disease VaccinesMiceMice, SCIDMutationProtein Structure, TertiaryRecombinant ProteinsConceptsB. burgdorferi sensu strictoBurgdorferi sensu strictoB. burgdorferi N40Treatment of miceOuter Surface ProteinsB. burgdorferi sensu lato genospeciesSurface protein AOuter surface protein ASCID miceMurine modelB. burgdorferi attachmentLyme diseaseMiceB. burgdorferiBorrelia afzeliiB. afzeliiTick gutBorrelia gariniiOspAVivoAdherenceAntiserumPresent studySurface proteinsGut
1999
Influence of Outer Surface Protein A Antibody onBorrelia burgdorferi within Feeding Ticks
de Silva A, Zeidner N, Zhang Y, Dolan M, Piesman J, Fikrig E. Influence of Outer Surface Protein A Antibody onBorrelia burgdorferi within Feeding Ticks. Infection And Immunity 1999, 67: 30-35. PMID: 9864192, PMCID: PMC96273, DOI: 10.1128/iai.67.1.30-35.1999.Peer-Reviewed Original ResearchConceptsAntibody levelsSalivary glandsAntibody titersOspA antibodiesBorrelia burgdorferiLow antibody levelsNumber of spirochetesDensity of spirochetesEnzyme-linked immunosorbentFeeding ticksSurface protein AAbility of spirochetesOuter surface protein AProtective epitopesCompetitive enzyme-linked immunosorbentOuter surface proteinsSpirochetal agentLyme diseaseAntibodiesB. burgdorferiTitersIxodes ticksGlandBurgdorferiSpirochetes
1997
Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice
Bockenstedt LK, Hodzic E, Feng S, Bourrel KW, de Silva A, Montgomery RR, Fikrig E, Radolf JD, Barthold SW. Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice. Infection And Immunity 1997, 65: 4661-4667. PMID: 9353047, PMCID: PMC175668, DOI: 10.1128/iai.65.11.4661-4667.1997.Peer-Reviewed Original ResearchConceptsChallenge infectionC antiserumImmunization studiesStrain-specific immunityAntibody-mediated immunityPassive immunization studiesImmune mouse serumSurface protein AOuter surface protein ADisease regressionInfected miceBorreliacidal activityC antibodySpirochete Borrelia burgdorferiAnimal modelsImmune serumMouse serumInfectionLyme borreliosisMiceHyperimmune serumOsp AImmunofluorescence studiesBorrelia burgdorferiSurface expressionOspA antibodies inhibit the acquisition of Borrelia burgdorferi by Ixodes ticks
de Silva AM, Fish D, Burkot TR, Zhang Y, Fikrig E. OspA antibodies inhibit the acquisition of Borrelia burgdorferi by Ixodes ticks. Infection And Immunity 1997, 65: 3146-3150. PMID: 9234767, PMCID: PMC175444, DOI: 10.1128/iai.65.8.3146-3150.1997.Peer-Reviewed Original ResearchConceptsOspA antibodiesB. burgdorferiPassive antibody transferB. burgdorferi infectionIxodes ticksSurface protein ABurgdorferi-infected miceB. burgdorferi-infected miceLarval infection ratesOuter surface protein AAntibody transferAntibody responseBurgdorferi infectionInfection rateInfected ticksMiceInhibitory effectAntibodiesLarval infectionBorrelia burgdorferiBurgdorferiInfectionLarval ticksReservoir competenceSpirochetesLyme Borreliosis in Transgenic Mice Tolerant to OspA from Borrelia burgdorferi 25015
Fikrig E, Barthold S, Chen M, Tao H, Ali-Salaam P, Bockenstedt L, Flavell R. Lyme Borreliosis in Transgenic Mice Tolerant to OspA from Borrelia burgdorferi 25015. The Journal Of Infectious Diseases 1997, 175: 1000-1003. PMID: 9086169, DOI: 10.1086/513958.Peer-Reviewed Original ResearchConceptsTransgenic miceLyme borreliosisC3H/HeN miceTolerance of miceSurface protein ABorrelia burgdorferi outer surface protein ASignificant arthritisOuter surface protein ALyme arthritisProtective immunityNontransgenic littermatesHeN miceOspA antibodiesDisease pathogenesisMiceArthritisB. burgdorferi N40OspABorreliosisCellular responsesProtein AResponseImmunizationPathogenesisLittermatesBorrelia burgdorferi enzyme-linked immunosorbent assay for discrimination of OspA vaccination from spirochete infection
Zhang YQ, Mathiesen D, Kolbert CP, Anderson J, Schoen RT, Fikrig E, Persing DH. Borrelia burgdorferi enzyme-linked immunosorbent assay for discrimination of OspA vaccination from spirochete infection. Journal Of Clinical Microbiology 1997, 35: 233-238. PMID: 8968914, PMCID: PMC229545, DOI: 10.1128/jcm.35.1.233-238.1997.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayVaccine failureFalse positivityAntigen preparationsExperimental animalsNatural infectionLyme disease vaccineB. burgdorferiExperimental animal modelsNegative enzyme-linked immunosorbent assayEnzyme-linked immunosorbentWhole-cell sonicateSurface protein AVaccinated subjectsLyme disease casesOuter surface protein AVaccinated personsFalse-positive resultsVaccine trialsOspA vaccinationSpirochete infectionDisease vaccineAnimal modelsHuman Lyme disease casesNegative isolatesSerologic diagnosis of canine and equine borreliosis: use of recombinant antigens in enzyme-linked immunosorbent assays
Magnarelli LA, Flavell RA, Padula SJ, Anderson JF, Fikrig E. Serologic diagnosis of canine and equine borreliosis: use of recombinant antigens in enzyme-linked immunosorbent assays. Journal Of Clinical Microbiology 1997, 35: 169-173. PMID: 8968901, PMCID: PMC229532, DOI: 10.1128/jcm.35.1.169-173.1997.Peer-Reviewed Original ResearchConceptsRecombinant antigensPolyvalent enzyme-linked immunosorbent assaysWhole-cell B. burgdorferiEnzyme-linked immunosorbent assayWestern blot analysisOuter surface protein ASensu strictoBlot analysisWhole cellsProtein AOSPFSerologic diagnosisBorrelia burgdorferi sensu strictoEquid seraBurgdorferi sensu strictoB. burgdorferiSurface protein AP41OspCWhole cell antigenEquine serumDog serumImmunosorbent assayOspBSerum samples
1996
Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice.
Bockenstedt LK, Fikrig E, Barthold SW, Flavell RA, Kantor FS. Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice. The Journal Of Immunology 1996, 157: 5496-502. PMID: 8955199, DOI: 10.4049/jimmunol.157.12.5496.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesEpitope MappingFemaleImmunization, PassiveImmunoglobulin GInterleukin-4LipoproteinsLymphocyte ActivationMiceMice, Inbred C3HMolecular Sequence DataPeptidesT-LymphocytesVaccines, SyntheticConceptsT cell epitopesCell epitopesPhase III efficacy studiesTick-borne spirochete Borrelia burgdorferiTreatment-resistant Lyme arthritisT cell responsesSurface protein AB-cell epitopesOuter surface protein ALyme arthritisChallenge infectionIgG productionN-terminal epitopeT cellsMultisystem disorderMurine modelSpirochete Borrelia burgdorferiSubunit vaccineEfficacy studiesCell responsesRecombinant vaccineLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi
1995
An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies.
Fikrig E, Liu B, Fu LL, Das S, Smallwood JI, Flavell RA, Persing DH, Schoen RT, Barthold SW, Malawista SE. An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies. The Journal Of Immunology 1995, 155: 5700-4. PMID: 7499856, DOI: 10.4049/jimmunol.155.12.5700.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupFemaleFrameshift MutationHumansLipoproteinsLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataProtein BindingSynovial FluidConceptsSurface protein AOuter surface protein ASynovial fluidChronic Lyme arthritisSynovial fluid samplesSeparate time pointsImmune effectivenessLyme arthritisPassive immunizationProtective antibodiesHuman infectionsHuman AbsProtein ATime pointsNatural infectionInfectionBorrelia burgdorferiMiceOnly factorHuman hostFluid samplesOspAInfected hostHuman materialMicrobial persistenceLyme 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 backgroundProgress Towards a Vaccine for Lyme Disease
Telford S, Fikrig E. Progress Towards a Vaccine for Lyme Disease. BioDrugs 1995, 4: 49-60. DOI: 10.1007/bf03259070.Peer-Reviewed Original ResearchLyme diseaseLyme disease vaccineSurface protein AOuter surface protein AProtective immunityPrototype vaccineCareful surveillanceClinical trialsChronic natureDisease vaccineSuch vaccinesMouse modelVaccinated hostAdvanced stageVaccineDiseaseInfectious ticksInfectionAntibodiesProtein AYearsMiceImmunityTrialsCircumvention 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 developmentSelection of variant Borrelia burgdorferi isolates from mice immunized with outer surface protein A or B
Fikrig E, Tao H, Barthold SW, Flavell RA. Selection of variant Borrelia burgdorferi isolates from mice immunized with outer surface protein A or B. Infection And Immunity 1995, 63: 1658-1662. PMID: 7729870, PMCID: PMC173206, DOI: 10.1128/iai.63.5.1658-1662.1995.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupCloning, MolecularFemaleGenes, BacterialGenetic VariationImmunoblottingLipoproteinsLyme DiseaseMiceMice, Inbred C3HRecombinant ProteinsSelection, GeneticSequence Analysis, DNAVaccinationConceptsSurface protein AOuter surface protein AProtective immunityProtective antibodiesIncomplete efficacyMiceMonoclonal antibodiesProtein ABorrelia burgdorferiB. burgdorferiAntigenic diversityOspBOspAVivo selective pressureImmunityAntibodiesB. burgdorferi isolatesBurgdorferiChallenge inoculationPoint mutationsMolecular basisVaccineInfectionEfficacy of Human Lyme Disease Vaccine Formulations in a Mouse Model
Telford SR, Kantor FS, Lobet Y, Barthold SW, Spielman A, Flavell RA, Fikrig E. Efficacy of Human Lyme Disease Vaccine Formulations in a Mouse Model. The Journal Of Infectious Diseases 1995, 171: 1368-1370. PMID: 7751719, DOI: 10.1093/infdis/171.5.1368.Peer-Reviewed Original ResearchConceptsMouse modelC3H/HeJ mouse modelLyme diseaseRecombinant outer surface protein APhase I human trialsPhase II trialSurface protein AUnvaccinated miceII trialVaccinated miceOuter surface protein AVaccine formulationsHuman trialsRecombinant OspAMiceBorrelia burgdorferiDiseaseTrialsMajor siteTrial sitesProtein ATicksImmunizationVaccineInfectionVaccination against Lyme disease caused by diverse Borrelia burgdorferi.
Fikrig E, Telford SR, Wallich R, Chen M, Lobet Y, Matuschka FR, Kimsey RB, Kantor FS, Barthold SW, Spielman A, Flavell RA. Vaccination against Lyme disease caused by diverse Borrelia burgdorferi. Journal Of Experimental Medicine 1995, 181: 215-221. PMID: 7807004, PMCID: PMC2191810, DOI: 10.1084/jem.181.1.215.Peer-Reviewed Original ResearchConceptsLyme diseaseB. burgdorferiVivo protection studiesBorrelia burgdorferi sensu latoSurface protein AOuter surface protein AVector-borne infectionsVaccine efficacyBurgdorferi sensu latoChallenge inoculumSpirochetal agentInfectionBorrelia burgdorferiDiseaseBurgdorferiOspAClassification systemProtection studiesProtein ADifferent geographic regionsSyringe injectionGeographic regionsVaccinationImmunizationVaccine
1994
Sera from Patients with Chronic Lyme Disease Protect Mice from Lyme Borreliosis
Fikrig E, Bockenstedt L, Barthold S, Chen M, Tao H, Salaam P, Telford S, Flavell R. Sera from Patients with Chronic Lyme Disease Protect Mice from Lyme Borreliosis. The Journal Of Infectious Diseases 1994, 169: 568-574. PMID: 8158028, DOI: 10.1093/infdis/169.3.568.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupChronic DiseaseFemaleHumansImmunization, PassiveImmunoblottingLipoproteinsLyme DiseaseMiceMice, Inbred C3HPolymerase Chain ReactionPrecipitin TestsConceptsStrong humoral responseLyme diseaseHumoral responseB. burgdorferiLate-stage Lyme diseaseLate Lyme diseaseElicit protective immunityChronic Lyme diseaseStrong antibody reactivityBorrelia burgdorferi challengeSurface protein AMost patientsOuter surface protein AProtective immunityImmune responsePatientsAntibody reactivityHuman antibodiesInfectionLyme borreliosisMiceDiseaseSerumNatural infectionAntibodies
1993
OspA vaccination of mice with established Borrelia burgdorferi infection alters disease but not infection
Fikrig E, Barthold SW, Flavell RA. OspA vaccination of mice with established Borrelia burgdorferi infection alters disease but not infection. Infection And Immunity 1993, 61: 2553-2557. PMID: 8500891, PMCID: PMC280883, DOI: 10.1128/iai.61.6.2553-2557.1993.Peer-Reviewed Original ResearchConceptsBooster injectionComplete Freund's adjuvantVaccination of miceMurine Lyme borreliosisMurine Lyme arthritisFinal booster injectionCommencement of vaccinationNumber of miceSurface protein APostexposure immunizationOuter surface protein APostexposure vaccinationLyme arthritisFreund's adjuvantActive immunizationHeart diseaseC3H miceIncomplete adjuvantVaccinationInfectionLyme borreliosisResolution phaseMiceAdjuvantBorrelia burgdorferi