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 ResearchMeSH KeywordsAnimalsAntigens, SurfaceBacterial Outer Membrane ProteinsCOVID-19COVID-19 VaccinesHumansLyme DiseaseMiceSARS-CoV-2ConceptsLyme 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
2009
Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent
Dai J, Wang P, Adusumilli S, Booth CJ, Narasimhan S, Anguita J, Fikrig E. Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent. Cell Host & Microbe 2009, 6: 482-492. PMID: 19917502, PMCID: PMC2843562, DOI: 10.1016/j.chom.2009.10.006.Peer-Reviewed Original ResearchConceptsArthropod-borne pathogensTick-borne BorreliaTick salivary proteinsTick proteinsB. burgdorferiLyme diseaseDisease agentsTick-borne illnessB. burgdorferi infectionLyme disease agentHuman vaccinesSalp15Infection of miceB. burgdorferi antigensMicrobial toxinsMammalian hostsBorrelia burgdorferiPathogensMechanism of actionBurgdorferi infectionProtect miceMedical importanceBurgdorferiProtective capacityMice
2007
Tick–host–pathogen interactions in Lyme borreliosis
Hovius JW, van Dam AP, Fikrig E. Tick–host–pathogen interactions in Lyme borreliosis. Trends In Parasitology 2007, 23: 434-438. PMID: 17656156, DOI: 10.1016/j.pt.2007.07.001.Peer-Reviewed Original ResearchConceptsVertebrate hostsB. burgdorferi survivalB. burgdorferi genesEnzootic life cycleSpirochete survivalGene productsB. burgdorferiArthropod vectorsGenesVector moleculesLife cycleDifferent environmentsHostBorrelia burgdorferiIxodes ticksTROSPATicksSpirochetal agentBurgdorferiLyme borreliosisMicrobesSalp15ExpressionSurvivalOuter Surface Protein B Is Critical for Borrelia burgdorferi Adherence and Survival within Ixodes Ticks
Neelakanta G, Li X, Pal U, Liu X, Beck DS, DePonte K, Fish D, Kantor FS, Fikrig E. Outer Surface Protein B Is Critical for Borrelia burgdorferi Adherence and Survival within Ixodes Ticks. PLOS Pathogens 2007, 3: e33. PMID: 17352535, PMCID: PMC1817655, DOI: 10.1371/journal.ppat.0030033.Peer-Reviewed Original Research
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 AReceptorsArthropodsBurgdorferiMammalsRepressionSpirochetesTicksBorrelia burgdorferi Changes Its Surface Antigenic Expression in Response to Host Immune Responses
Liang FT, Yan J, Mbow ML, Sviat SL, Gilmore RD, Mamula M, Fikrig E. Borrelia burgdorferi Changes Its Surface Antigenic Expression in Response to Host Immune Responses. Infection And Immunity 2004, 72: 5759-5767. PMID: 15385475, PMCID: PMC517580, DOI: 10.1128/iai.72.10.5759-5767.2004.Peer-Reviewed Original ResearchConceptsSurface antigenic expressionAntigenic expressionImmune attackImmune responseSevere combined immunodeficiency miceHostile immune environmentVigorous immune responseB. burgdorferiCombined immunodeficiency miceHost immune responseOspC antibodiesOuter surface protein CImmune environmentDecorin-binding protein AImmunocompetent miceImmune conditionsImmunodeficiency miceSurface protein CImmune pressureVlsE expressionLyme disease spirocheteProtein CBorrelia burgdorferiOspC expressionMammalian infectionBorrelia burgdorferi outer surface protein (osp) B expression independent of ospA
Liang FT, Caimano MJ, Radolf JD, Fikrig E. Borrelia burgdorferi outer surface protein (osp) B expression independent of ospA. Microbial Pathogenesis 2004, 37: 35-40. PMID: 15194158, DOI: 10.1016/j.micpath.2004.02.007.Peer-Reviewed Original ResearchAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiDisease Models, AnimalGene Expression Regulation, BacterialLipoproteinsLyme DiseaseMiceMice, Inbred BALB CMice, SCIDPromoter Regions, GeneticRNA, BacterialRNA, MessengerTicksTranscription, GeneticEssential Role for OspA/B in the Life Cycle of the Lyme Disease Spirochete
Yang XF, Pal U, Alani SM, Fikrig E, Norgard MV. Essential Role for OspA/B in the Life Cycle of the Lyme Disease Spirochete. Journal Of Experimental Medicine 2004, 199: 641-648. PMID: 14981112, PMCID: PMC2213294, DOI: 10.1084/jem.20031960.Peer-Reviewed Original Research
2003
An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine
Schoen RT, Deshefy-Longhi T, Van-Hoecke C, Buscarino C, Fikrig E. An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine. Clinical Therapeutics 2003, 25: 210-224. PMID: 12637121, DOI: 10.1016/s0149-2918(03)90027-0.Peer-Reviewed Original ResearchConceptsLyme disease vaccineFirst booster doseSecond booster doseBooster doseAdverse eventsBooster dosesPrimary seriesMonth 24Disease vaccineClinical trialsEfficacy trialsImmune responseIncidence of AEsPattern of AEsLyme diseaseMost adverse eventsGeometric mean titersTotal IgG antibodiesProportion of subjectsPositive test resultsSeroprotective levelsBooster vaccinationMonth 36Third vaccinationDiary cards
2002
The Lyme Disease Vaccine Takes Its Toll
Thomas V, Fikrig E. The Lyme Disease Vaccine Takes Its Toll. Vector-Borne And Zoonotic Diseases 2002, 2: 217-222. PMID: 12804162, DOI: 10.1089/153036602321653798.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiHumansLipoproteinsLyme DiseaseLyme Disease VaccinesMembrane GlycoproteinsMiceMice, KnockoutReceptors, Cell SurfaceToll-Like Receptor 1Toll-Like Receptor 2Toll-Like ReceptorsConceptsTLR2-deficient miceToll-like receptorsPathogen-associated molecular patternsOspA antibodiesSpecific Toll-like receptorsBorrelia burgdorferi outer surface proteinDetectable humoral responseMolecular patternsProtective immune responseLyme disease vaccineDistinct pathogen-associated molecular patternsVaccine recipientsHumoral responseOspA vaccineCell surface expressionOspA vaccinationImmune responseDisease vaccineInnate responseTLR2Protective responseOuter surface proteinsTLR1Lyme diseaseDevelopment of responsesComparative reactivity of human sera to recombinant VlsE and other Borrelia burgdorferi antigens in class-specific enzyme-linked immunosorbent assays for Lyme borreliosis
Magnarelli LA, Lawrenz M, Norris SJ, Fikrig E. Comparative reactivity of human sera to recombinant VlsE and other Borrelia burgdorferi antigens in class-specific enzyme-linked immunosorbent assays for Lyme borreliosis. Journal Of Medical Microbiology 2002, 51: 649-655. PMID: 12171295, DOI: 10.1099/0022-1317-51-8-649.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayIgG antibodiesErythema migransIgM antibodiesLyme borreliosisPhysician-diagnosed erythema migransOnset of illnessVlsE antigenB. burgdorferi infectionBorrelia burgdorferi antigensEnzyme-linked immunosorbentHuman granulocytic ehrlichiosisHuman serumOuter surface protein CRheumatoid arthritisBorrelia burgdorferi sensu strictoOral infectionBurgdorferi infectionFalse-positive reactionsBurgdorferi sensu strictoSera crossLouse-borneLaboratory diagnosisNormal serumGranulocytic ehrlichiosisHyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice
Alexopoulou L, Thomas V, Schnare M, Lobet Y, Anguita J, Schoen RT, Medzhitov R, Fikrig E, Flavell RA. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nature Medicine 2002, 8: 878-884. PMID: 12091878, DOI: 10.1038/nm732.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiCell SeparationCells, CulturedDrosophila ProteinsHumansInterleukinsLipoproteinsLyme Disease VaccinesMacrophagesMembrane GlycoproteinsMiceMice, KnockoutReceptors, Cell SurfaceSignal TransductionToll-Like Receptor 1Toll-Like Receptor 2Toll-Like ReceptorsConceptsToll-like receptor 1Less tumor necrosis factorTLR2-deficient miceLow antibody titersLyme disease vaccineTumor necrosis factorLow cell surface expressionOuter surface lipoproteinsVaccine recipientsAntibody titersInterleukin-6Cell surface expressionNecrosis factorOspA vaccinationDisease vaccineLow respondersInnate responseTLR2Low titersReceptor 1Substantial titersVaccinationMiceTLR1Borrelia burgdorferi
2001
Borrelia burgdorferi-Induced Inflammation Facilitates Spirochete Adaptation and Variable Major Protein-Like Sequence Locus Recombination
Anguita J, Thomas V, Samanta S, Persinski R, Hernanz C, Barthold S, Fikrig E. Borrelia burgdorferi-Induced Inflammation Facilitates Spirochete Adaptation and Variable Major Protein-Like Sequence Locus Recombination. The Journal Of Immunology 2001, 167: 3383-3390. PMID: 11544329, PMCID: PMC4309988, DOI: 10.4049/jimmunol.167.6.3383.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial ProteinsBase SequenceBorrelia burgdorferiCD4-Positive T-LymphocytesDNA, BacterialGene Expression RegulationImmune SeraImmunocompetenceInflammationInterferon-gammaInterleukin-12LipoproteinsLyme DiseaseMiceMice, Inbred C3HMice, KnockoutMolecular Sequence DataReceptors, InterferonRecombination, GeneticSequence AlignmentSequence Homology, Nucleic AcidConceptsImmunocompetent miceDeficient miceB. burgdorferi N40IFN-gammaRMurine immune responseIFN-gamma-mediated responsesIFN-gamma-mediated signalsSpirochetal burdensSpirochete clearanceIL-12Immune responseIFN-gammaControl animalsDifferential immunoscreeningMice resultsMiceVariable major proteinsRT-PCRVivo adaptationB. burgdorferiClearanceBorrelia burgdorferi gene expressionB. burgdorferi survivalAdministrationVivoInhibition 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 proteinsGutOspA Immunization Decreases Transmission of Borrelia burgdorferi Spirochetes from Infected Peromyscus leucopus Mice to Larval Ixodes scapularis Ticks
Tsao J, Barbour A, Luke C, Fikrig E, Fish D. OspA Immunization Decreases Transmission of Borrelia burgdorferi Spirochetes from Infected Peromyscus leucopus Mice to Larval Ixodes scapularis Ticks. Vector-Borne And Zoonotic Diseases 2001, 1: 65-74. PMID: 12653137, DOI: 10.1089/153036601750137705.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, WildAntibodies, BacterialAntigens, SurfaceArachnid VectorsBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiDisease ReservoirsDose-Response Relationship, ImmunologicEnzyme-Linked Immunosorbent AssayFluorescent Antibody Technique, DirectHost-Parasite InteractionsIxodesLarvaLipoproteinsLyme DiseasePeromyscusConceptsControl miceUninfected larval ticksInfection prevalenceLarval Ixodes scapularis ticksB. burgdorferiNumber of spirochetesEnzyme-linked immunosorbentBorrelia burgdorferi spirochetesLevel of immunizationReservoir hostsConcentration of antibodyBorrelia burgdorferi transmissionIxodes scapularis ticksSecond vaccinationImmunized miceInfected miceLarval ticksPrior infectionVaccination programSubsequent riskDecrease transmissionOspA vaccinationDirect immunofluorescenceImmune responseXenodiagnostic ticks
2000
Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A
Pal U, de Silva A, Montgomery R, Fish D, Anguita J, Anderson J, Lobet Y, Fikrig E. Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A. Journal Of Clinical Investigation 2000, 106: 561-569. PMID: 10953031, PMCID: PMC380253, DOI: 10.1172/jci9427.Peer-Reviewed Original ResearchBorrelia burgdorferi Gene Expression In Vivo and Spirochete Pathogenicity
Anguita J, Samanta S, Revilla B, Suk K, Das S, Barthold S, Fikrig E. Borrelia burgdorferi Gene Expression In Vivo and Spirochete Pathogenicity. Infection And Immunity 2000, 68: 1222-1230. PMID: 10678930, PMCID: PMC97271, DOI: 10.1128/iai.68.3.1222-1230.2000.Peer-Reviewed Original ResearchConceptsC3H/HeN miceBorrelia burgdorferi spirochetesLyme disease pathogenesisNonpathogenic spirochetesSpirochete disseminationHumoral responseImmunocompetent miceHeN miceSCID miceC3H miceImmunodeficient miceImmune serumDisease pathogenesisCarditisArthritisMiceGene expressionGenomic expression libraryDiseaseB. burgdorferiB. burgdorferi N40Borrelia burgdorferi gene expressionMammalian infectionSubsequent developmentInfection
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 ticksGlandBurgdorferiSpirochetesThe Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis
Akin E, McHugh G, Flavell R, Fikrig E, Steere A. The Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis. Infection And Immunity 1999, 67: 173-181. PMID: 9864212, PMCID: PMC96293, DOI: 10.1128/iai.67.1.173-181.1999.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntigens, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupChildChild, PreschoolFemaleHumansImmunoglobulin GLipoproteinsLongitudinal StudiesLyme DiseaseMaleMiddle AgedSeverity of Illness IndexConceptsAntibody responseIgG antibodiesEarly arthritisLyme arthritisIgG responsesEarly infectionDuration of arthritisChronic Lyme arthritisIgG antibody responseSerial serum samplesBorrelia burgdorferi proteinsSubsequent arthritisB. burgdorferi proteinsSurface protein CC-terminal epitopeImmune responseArthritisSubsequent severityNatural historyLyme diseasePatientsSerum samplesImmunoglobulin GProtein CInfection