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 transmissionmRNA vaccination of rabbits alters the fecundity, but not the attachment, of adult Ixodes scapularis
Matias J, Cui Y, Lynn G, DePonte K, Mesquita E, Muramatsu H, Alameh M, Dwivedi G, Tam Y, Pardi N, Weissman D, Fikrig E. mRNA vaccination of rabbits alters the fecundity, but not the attachment, of adult Ixodes scapularis. Scientific Reports 2024, 14: 496. PMID: 38177212, PMCID: PMC10766947, DOI: 10.1038/s41598-023-50389-6.Peer-Reviewed Original Research
2021
mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent
Sajid A, Matias J, Arora G, Kurokawa C, DePonte K, Tang X, Lynn G, Wu MJ, Pal U, Strank NO, Pardi N, Narasimhan S, Weissman D, Fikrig E. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Science Translational Medicine 2021, 13: eabj9827. PMID: 34788080, DOI: 10.1126/scitranslmed.abj9827.Peer-Reviewed Original ResearchConceptsTick-borne infectionsTick-borne infectious diseaseEngorgement weightDisease agentsTicksTick exposureLyme disease agentGuinea pigsTick biteNormal blood mealBlood mealNucleoside-modified mRNALyme diseasePigsLocal rednessMRNA vaccinationMRNA vaccinesBite siteSalivary proteinsPrevents transmissionInfectious diseasesDiseaseVaccineResistanceEffective induction
2019
Protective Immunity and New Vaccines for Lyme Disease
Gomes-Solecki M, Arnaboldi PM, Backenson PB, Benach JL, Cooper CL, Dattwyler RJ, Diuk-Wasser M, Fikrig E, Hovius JW, Laegreid W, Lundberg U, Marconi RT, Marques AR, Molloy P, Narasimhan S, Pal U, Pedra JHF, Plotkin S, Rock DL, Rosa P, Telford SR, Tsao J, Yang XF, Schutzer SE. Protective Immunity and New Vaccines for Lyme Disease. Clinical Infectious Diseases 2019, 70: 1768-1773. PMID: 31620776, PMCID: PMC7155782, DOI: 10.1093/cid/ciz872.Peer-Reviewed Original ResearchConceptsLyme diseaseCommon tick-borne illnessTick-borne illnessB. burgdorferi infectionBorrelia burgdorferi sensu latoMechanism of actionDirect vaccinationB. burgdorferi proteinsProtective immunityBurgdorferi sensu latoVaccination strategiesBurgdorferi infectionFirst vaccineImmune pathwaysNew vaccinesNumber of casesTick immunityDiseaseVaccineB. burgdorferiHuman hostTick proteinsInfectionImmunityPathogen transmission
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 capacityMiceInflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy
Demento SL, Eisenbarth SC, Foellmer HG, Platt C, Caplan MJ, Saltzman W, Mellman I, Ledizet M, Fikrig E, Flavell RA, Fahmy TM. Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 2009, 27: 3013-3021. PMID: 19428913, PMCID: PMC2695996, DOI: 10.1016/j.vaccine.2009.03.034.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAnimalsAntibody FormationCarrier ProteinsCD8-Positive T-LymphocytesDendritic CellsLactic AcidLipopolysaccharidesMiceMice, Inbred C57BLNanoparticlesNLR Family, Pyrin Domain-Containing 3 ProteinPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerVaccinationViral Envelope ProteinsWest Nile FeverWest Nile Virus VaccinesConceptsPattern recognition receptorsToll-like receptorsInflammasome activationInnate immune system activationEffective adaptive immune responseIntracellular pattern recognition receptorsAntigen-presenting cellsAdaptive immune responsesWest Nile encephalitisImmune system activationInnate immune pathwaysWild-type macrophagesDendritic cellsCellular immunityVaccination approachesVaccine efficacyIL-1betaNLRP3 inflammasomeAdjuvant systemImmune responsePotent new approachMurine modelInflammasome activitySystem activationImmune pathways
2004
Immunity to West Nile virus
Wang T, Fikrig E. Immunity to West Nile virus. Current Opinion In Immunology 2004, 16: 519-523. PMID: 15245749, DOI: 10.1016/j.coi.2004.05.008.Peer-Reviewed Original ResearchConceptsWN virus infectionWest Nile virusVirus infectionImportant public health concernWN virusNile virusPublic health concernActive immunizationPassive transferEffective vaccineT cellsMurine susceptibilityHealth concernExperimental modelEnvelope proteinVirusInfectionImmunityRecent studiesImmunotherapyImmunizationPathogenesisTherapyVaccine
2003
Immunoassay Targeting Nonstructural Protein 5 To Differentiate West Nile Virus Infection from Dengue and St. Louis Encephalitis Virus Infections and from Flavivirus Vaccination
Wong SJ, Boyle RH, Demarest VL, Woodmansee AN, Kramer LD, Li H, Drebot M, Koski RA, Fikrig E, Martin DA, Shi PY. Immunoassay Targeting Nonstructural Protein 5 To Differentiate West Nile Virus Infection from Dengue and St. Louis Encephalitis Virus Infections and from Flavivirus Vaccination. Journal Of Clinical Microbiology 2003, 41: 4217-4223. PMID: 12958248, PMCID: PMC193845, DOI: 10.1128/jcm.41.9.4217-4223.2003.Peer-Reviewed Original ResearchConceptsSt. Louis encephalitis virus infectionEncephalitis virus infectionWest Nile virusWNV infectionVirus infectionFlavivirus vaccinationWest Nile virus infectionNatural WNV infectionWNV structural proteinsDetection of antibodiesBlood transfusionRecent infectionOrgan transplantationSerologic assaysImmune responseDengue virusInfectionProtein 3Nonstructural protein 3Nile virusNatural transmissionProtein 5Structural proteinsLack specificityFrequent epidemicsAn 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
Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis
IJdo JW, Wu C, Telford SR, Fikrig E. Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis. Infection And Immunity 2002, 70: 5295-5298. PMID: 12183586, PMCID: PMC128253, DOI: 10.1128/iai.70.9.5295-5298.2002.Peer-Reviewed Original ResearchConceptsP44 geneDifferential expressionHuman granulocytic ehrlichiosisGene familyAntigenic variationHGE bacteriaTransmission feedingGranulocytic ehrlichiosisGenesHypervariable regionInfected C3H miceP44 expressionTick transmissionExpressionSCID miceC3H miceHGE infectionMurine modelInfected ticksSalivary glandsNymphal ticksMiceTicksEhrlichiosisBacteria
2001
Reactivity of dog sera to whole-cell or recombinant antigens of Borrelia burgdorferi by ELISA and immunoblot analysis
Magnarelli LA, Levy SA, Ijdo JW, Wu C, Padula SJ, Fikrig E. Reactivity of dog sera to whole-cell or recombinant antigens of Borrelia burgdorferi by ELISA and immunoblot analysis. Journal Of Medical Microbiology 2001, 50: 889-895. PMID: 11599738, DOI: 10.1099/0022-1317-50-10-889.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayWhole cell antigenRecombinant antigensB. burgdorferiNon-vaccinated dogsPolyvalent enzyme-linked immunosorbent assaysCanine borreliosisTick-infested areasTotal immunoglobulinWhole-cell B. burgdorferiAntibody titresBorrelia burgdorferi sensu strictoVaccinated dogsJoint disordersImmune responseBurgdorferi sensu strictoAntigenImmunosorbent assaySerumDogsNatural infection
1997
Immunization against the agent of human granulocytic ehrlichiosis in a murine model.
Sun W, IJdo JW, Telford SR, Hodzic E, Zhang Y, Barthold SW, Fikrig E. Immunization against the agent of human granulocytic ehrlichiosis in a murine model. Journal Of Clinical Investigation 1997, 100: 3014-3018. PMID: 9399947, PMCID: PMC508513, DOI: 10.1172/jci119855.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisGranulocytic ehrlichiosisC3H/HeN miceAgent of HGEMimic human diseaseTick-borne infectionsTransient neutropeniaHeN miceMurine modelPolymorphonuclear leukocytesTick-borne pathogensAoHGEMiceImmunityEhrlichiosisSyringe inoculationHuman diseasesAgentsNeutropeniaImmunizationInfectionLeukocytesDiseaseAntibodies
1995
Serologic responses of dogs naturally exposed to or vaccinated against Borrelia burgdorferi infection.
Barthold S, Levy S, Fikrig E, Bockenstedt L, Smith A. Serologic responses of dogs naturally exposed to or vaccinated against Borrelia burgdorferi infection. Journal Of The American Veterinary Medical Association 1995, 207: 1435-40. PMID: 7493871, DOI: 10.2460/javma.1995.207.11.1435.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBiological AssayBlotting, WesternBorrelia burgdorferi GroupDog DiseasesDogsEnzyme-Linked Immunosorbent AssayFemaleImmune SeraImmunoglobulin GImmunoglobulin MLyme DiseaseMaleMiceMice, Inbred C3HVaccinationConceptsSerologic responseAntibiotic treatmentVaccinated dogsRecombinant outer surface proteinPassive protective activityBorrelia burgdorferi infectionMeans of ELISAImmunoblot analysisSeronegative dogsClinical responseSerologic testingClinical criteriaControl dogsAntibody responseMouse protectionB burgdorferiClinical trialsBurgdorferi infectionInfected dogsELISA titersProtective activityOuter surface proteinsUseful antigenDogsBorrelia burgdorferiSelection 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
1993
Inability of truncated recombinant Osp A proteins to elicit protective immunity to Borrelia burgdorferi in mice.
Bockenstedt LK, Fikrig E, Barthold SW, Kantor FS, Flavell RA. Inability of truncated recombinant Osp A proteins to elicit protective immunity to Borrelia burgdorferi in mice. The Journal Of Immunology 1993, 151: 900-6. PMID: 8335917, DOI: 10.4049/jimmunol.151.2.900.Peer-Reviewed Original ResearchConceptsA antibodiesOsp AProtective immunityMurine immune responseBorrelia burgdorferiElicit protective immunityGroups of miceDevelopment of antibodiesOuter surface protein A.Vaccine AgsChallenge infectionPassive immunizationActive immunizationImmune responseEtiologic agentIndirect immunofluorescenceLyme diseaseMiceVaccinationA antiseraAntibodiesImmunityConformational epitopesA proteinImmunizationOspA 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
1992
Borrelia burgdorferi strain 25015: characterization of outer surface protein A and vaccination against infection.
Fikrig E, Barthold SW, Persing DH, Sun X, Kantor FS, Flavell RA. Borrelia burgdorferi strain 25015: characterization of outer surface protein A and vaccination against infection. The Journal Of Immunology 1992, 148: 2256-60. PMID: 1545130, DOI: 10.4049/jimmunol.148.7.2256.Peer-Reviewed Original ResearchConceptsSurface protein AOuter surface protein ABorrelia burgdorferi strain N40Vaccination of miceB. burgdorferiImmunized miceVaccination experimentsIntradermal challengeVaccine candidatesCerebrospinal fluidMiceProtein AStrain N40VaccinationStrain 297OspA geneBurgdorferiOspACD16NeuroborreliosisPatientsInfectionLong-term protection of mice from Lyme disease by vaccination with OspA
Fikrig E, Barthold SW, Kantor FS, Flavell RA. Long-term protection of mice from Lyme disease by vaccination with OspA. Infection And Immunity 1992, 60: 773-777. PMID: 1541551, PMCID: PMC257553, DOI: 10.1128/iai.60.3.773-777.1992.Peer-Reviewed Original Research