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 platformRepeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding
Narasimhan S, Booth C, Philipp M, Fikrig E, Embers M. Repeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding. Pathogens 2023, 12: 132. PMID: 36678479, PMCID: PMC9861725, DOI: 10.3390/pathogens12010132.Peer-Reviewed Original ResearchNon-human primatesImmune responseLyme diseaseTick transmissionAnimal modelsGuinea pigsNon-human primate modelProtective immune responseTick feedingTick infestationRobust immune responseTick salivary antigensElicit immune responsesHuman Lyme diseaseClinical manifestationsHuman pathogensPrimate modelSalivary antigensNon-natural hostsVaccine targetsDiseaseVaccine discoveryTick resistanceBorreliaNatural host
2022
Use of host lipids by the Lyme disease spirochete may lead to biomarkers
Arora G, Hart T, Fikrig E. Use of host lipids by the Lyme disease spirochete may lead to biomarkers. Journal Of Clinical Investigation 2022, 132: e158254. PMID: 35289311, PMCID: PMC8920323, DOI: 10.1172/jci158254.Peer-Reviewed Original ResearchConceptsB. burgdorferi infectionLyme diseaseBurgdorferi infectionCareful clinical assessmentCommon tick-borne diseaseAnti-lipid antibodiesProduction of antibodiesTick-borne diseaseHost lipidsAntibody titersLyme disease agent Borrelia burgdorferiClinical assessmentCurrent biomarkersMurine modelDiseaseSerum samplesLyme disease spirocheteAntibodiesBorrelia burgdorferiInfectionBiomarkersPatientsLipidsSyphilisPhosphatidic acid
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
2020
An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
Cao Y, Rosen C, Arora G, Gupta A, Booth CJ, Murfin KE, Cerny J, Lopez A, Chuang YM, Tang X, Pal U, Ring A, Narasimhan S, Fikrig E. An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector. Infection And Immunity 2020, 88: 10.1128/iai.00426-20. PMID: 32928964, PMCID: PMC7671890, DOI: 10.1128/iai.00426-20.Peer-Reviewed Original ResearchConceptsTick gutTick bite siteVector-host interfaceAbility of spirochetesProtein disulfide isomerase A3Infected vertebrate hostsInflammatory responseBite siteLyme diseaseVertebrate hostsGutTick proteinsAdditional targetsMiceSpirochete life cycleSpirochete survivalArthropod vectorsSpirochetesRNA interferenceIllnessTicksA human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis
Gupta A, Arora G, Rosen CE, Kloos Z, Cao Y, Cerny J, Sajid A, Hoornstra D, Golovchenko M, Rudenko N, Munderloh U, Hovius JW, Booth CJ, Jacobs-Wagner C, Palm NW, Ring AM, Fikrig E. A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis. PLOS Pathogens 2020, 16: e1009030. PMID: 33175909, PMCID: PMC7657531, DOI: 10.1371/journal.ppat.1009030.Peer-Reviewed Original ResearchConceptsPeptidoglycan recognition protein 1B. burgdorferi infectionB. burgdorferiBurgdorferi infectionHost responseLow serum IgG levelsCommon vector-borne illnessDiverse host responsesSerum IgG levelsProtein 1Vector-borne illnessImmune dysregulationIgG levelsBorreliacidal activityBurgdorferi sensu latoHuman extracellular proteinsSpirochete burdenTick biteB. burgdorferi sensu latoSpirochete Borrelia burgdorferiNervous systemLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi
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 transmissionPolymicrobial Nature of Tick-Borne Diseases
Sanchez-Vicente S, Tagliafierro T, Coleman J, Benach J, Tokarz R, Azad A, Fikrig E, Munderloh U, Telford S. Polymicrobial Nature of Tick-Borne Diseases. MBio 2019, 10: e02055-19. PMID: 31506314, PMCID: PMC6737246, DOI: 10.1128/mbio.02055-19.Peer-Reviewed Original ResearchConceptsPolymicrobial infectionsClinical spectrumTick-borne diseasesFatal infectionPowassan virusDisproportionate incidenceTick-borne diseaseDifficult diagnosisNew pathogensNew agentsPolymicrobial natureDisease severityInfectionDiseaseLyme diseasePrevalent pathogenBorreliaHigh rateIncidenceDiagnosisSeverityRickettsiaTick vectorVirusClimate change
2018
Host-specific expression of Ixodes scapularis salivary genes
Narasimhan S, Booth CJ, DePonte K, Wu MJ, Liang X, Mohanty S, Kantor F, Fikrig E. Host-specific expression of Ixodes scapularis salivary genes. Ticks And Tick-borne Diseases 2018, 10: 386-397. PMID: 30545615, DOI: 10.1016/j.ttbdis.2018.12.001.Peer-Reviewed Original ResearchConceptsVector-host interactionsTick infestationI. scapularisReservoir hostsNon-reservoir hostsHost-specific expressionRodent reservoir hostsInfected ticksPathogen transmissionZoonotic cycleSalivary genesIxodes scapularisTicksNatural hostScapularisInfestationTick biteLyme diseaseBorrelia burgdorferiLarval stagesPathogensHostPeromyscus leucopusStrong immune responseSalivary transcriptomeDirect Diagnostic Tests for Lyme Disease
Schutzer SE, Body BA, Boyle J, Branson BM, Dattwyler RJ, Fikrig E, Gerald NJ, Gomes-Solecki M, Kintrup M, Ledizet M, Levin AE, Lewinski M, Liotta LA, Marques A, Mead PS, Mongodin EF, Pillai S, Rao P, Robinson WH, Roth KM, Schriefer ME, Slezak T, Snyder JL, Steere AC, Witkowski J, Wong SJ, Branda JA. Direct Diagnostic Tests for Lyme Disease. Clinical Infectious Diseases 2018, 68: 1052-1057. PMID: 30307486, PMCID: PMC6399434, DOI: 10.1093/cid/ciy614.Peer-Reviewed Original Research
2017
Advances in Serodiagnostic Testing for Lyme Disease Are at Hand
Branda JA, Body BA, Boyle J, Branson BM, Dattwyler RJ, Fikrig E, Gerald NJ, Gomes-Solecki M, Kintrup M, Ledizet M, Levin AE, Lewinski M, Liotta LA, Marques A, Mead PS, Mongodin EF, Pillai S, Rao P, Robinson WH, Roth KM, Schriefer ME, Slezak T, Snyder J, Steere AC, Witkowski J, Wong SJ, Schutzer SE. Advances in Serodiagnostic Testing for Lyme Disease Are at Hand. Clinical Infectious Diseases 2017, 66: 1133-1139. PMID: 29228208, PMCID: PMC6019075, DOI: 10.1093/cid/cix943.Peer-Reviewed Original ResearchConceptsSerodiagnostic testingEnzyme immunoassayLyme diseaseIndirect fluorescence antibodySerologic assaysImmunoglobulin MEarly infectionFluorescence antibodyTesting protocolAlternative testing protocolsBorrelia burgdorferiB. burgdorferiWestern immunoblotAntigenDiseaseAntibodiesBurgdorferiLow sensitivitySynthetic peptidesAssays
2014
Borrelia miyamotoi sensu lato Seroreactivity and Seroprevalence in the Northeastern United States - Volume 20, Number 7—July 2014 - Emerging Infectious Diseases journal - CDC
Krause PJ, Narasimhan S, Wormser GP, Barbour AG, Platonov AE, Brancato J, Lepore T, Dardick K, Mamula M, Rollend L, Steeves TK, Diuk-Wasser M, Usmani-Brown S, Williamson P, Sarksyan DS, Fikrig E, Fish D, . Borrelia miyamotoi sensu lato Seroreactivity and Seroprevalence in the Northeastern United States - Volume 20, Number 7—July 2014 - Emerging Infectious Diseases journal - CDC. Emerging Infectious Diseases 2014, 20: 1183-1190. PMID: 24960072, PMCID: PMC4073859, DOI: 10.3201/eid2007.131587.Peer-Reviewed Original ResearchConceptsB. burgdorferiInfectious Diseases journal - CDCSeroprevalence of IgGB. burgdorferi antigensLyme disease endemic areaDisease-endemic areasAntibody testingHealthy personsLyme diseaseSerum samplesSeroprevalenceBurgdorferiInfectionSame tickUnited StatesSensu latoArea residentsPersonsBorrelia spSeroreactivityIgGAntigenDiseaseSerum
2013
Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
Narasimhan S, Perez O, Mootien S, DePonte K, Koski RA, Fikrig E, Ledizet M. Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis. PLOS ONE 2013, 8: e68012. PMID: 23874485, PMCID: PMC3706618, DOI: 10.1371/journal.pone.0068012.Peer-Reviewed Original ResearchConceptsTick gutBlood mealVertebrate hostsTick gut proteinsPathogen transmissionBorrelia burgdorferi transmissionAnticoagulation strategiesThrombin inhibitory activityHemostatic mechanismThrombin inhibitorsMammalian coagulationIxodes scapularisMammalian hostsTick salivaLyme diseaseKey enzymeGut proteinsBorrelia burgdorferiTick feedingHost bloodHours of feedingGutFunctional suiteTick proteinsHuman pathogens
2011
Molecular Interactions that Enable Movement of the Lyme Disease Agent from the Tick Gut into the Hemolymph
Zhang L, Zhang Y, Adusumilli S, Liu L, Narasimhan S, Dai J, Zhao YO, Fikrig E. Molecular Interactions that Enable Movement of the Lyme Disease Agent from the Tick Gut into the Hemolymph. PLOS Pathogens 2011, 7: e1002079. PMID: 21695244, PMCID: PMC3111543, DOI: 10.1371/journal.ppat.1002079.Peer-Reviewed Original ResearchConceptsLyme disease agentB. burgdorferi burdenTick gutOuter surface lipoproteinsTick gut proteinsSalivary gland infectionIxodes scapularis ticksInfection resultsMouse infectionDisease agentsGland infectionLyme diseaseBorrelia burgdorferiScapularis ticksB. burgdorferiCausative agentInfectionBurgdorferiGutGut proteinsSpirochetesTick hemolymphTicksAgentsHemolymph
2010
Lyme borreliosis vaccination: the facts, the challenge, the future
Schuijt TJ, Hovius JW, van der Poll T, van Dam AP, Fikrig E. Lyme borreliosis vaccination: the facts, the challenge, the future. Trends In Parasitology 2010, 27: 40-47. PMID: 20594913, DOI: 10.1016/j.pt.2010.06.006.Peer-Reviewed Original ResearchConceptsBorrelia burgdorferi sensu lato groupPrevalent arthropod-borne diseaseAnti-tick vaccinesLyme borreliosisArthropod-borne diseaseSensu lato groupTick proteinsTick vectorIxodes ticksNovel vaccination strategiesTicksMammalian hostsVaccination strategiesLyme diseaseVaccine candidatesBorreliosisBorrelia antigensVaccineAntigenDiseaseBorreliaOuter membrane proteinsWestern worldFuture candidatesSpirochetes
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 capacityMicePassage through Ixodes scapularis Ticks Enhances the Virulence of a Weakly Pathogenic Isolate of Borrelia burgdorferi
Adusumilli S, Booth CJ, Anguita J, Fikrig E. Passage through Ixodes scapularis Ticks Enhances the Virulence of a Weakly Pathogenic Isolate of Borrelia burgdorferi. Infection And Immunity 2009, 78: 138-144. PMID: 19822652, PMCID: PMC2798202, DOI: 10.1128/iai.00470-09.Peer-Reviewed Original ResearchConceptsIxodes scapularis ticksCommon tick-borne illnessScapularis ticksTick-borne illnessB. burgdorferi sensu strictoC3H miceBurgdorferi sensu strictoLyme diseaseMiceHigh expression levelsBorrelia burgdorferiB. burgdorferiTick engorgementExpression levelsSpirochetesDiseaseArray analysisSyringe inoculationBurgdorferiPathogenic isolatesIsolatesI. scapularisArthritisVirulencePathogenesisLate Manifestations of Lyme Borreliosis
Hovius J, van Dam A, Fikrig E. Late Manifestations of Lyme Borreliosis. 2009, 9-25. DOI: 10.1128/9781555815486.ch2.Peer-Reviewed Original ResearchLyme borreliosisObjective clinical manifestationsFrequent clinical signsB. burgdorferiB. burgdorferi infectionHost immune responseCommon vector-borne diseaseClinical manifestationsErythema migransAntibiotic treatmentClinical signsBurgdorferi infectionImmune responsePositive culturesLate manifestationTick-borne pathogensLyme diseaseBorreliosisBorrelia burgdorferiDiseaseCausative agentB. afzeliiB. gariniiInfected tissuesBurgdorferiInhibition of Neutrophil Function by Two Tick Salivary Proteins
Guo X, Booth CJ, Paley MA, Wang X, DePonte K, Fikrig E, Narasimhan S, Montgomery RR. Inhibition of Neutrophil Function by Two Tick Salivary Proteins. Infection And Immunity 2009, 77: 2320-2329. PMID: 19332533, PMCID: PMC2687334, DOI: 10.1128/iai.01507-08.Peer-Reviewed Original ResearchConceptsPolymorphonuclear leukocytesPMN functionNumber of PMNPMN integrinsPMN adherenceNeutrophil functionSpirochete burdenTick salivary proteinsTick salivaLyme diseaseTick attachmentSalivary glandsBorrelia burgdorferiTick feedingCausative agentReduced levelsInhibitory proteinSalivaBlood mealAntihemostatic activityInfectionInhibitionSalivary proteinsHematophagous arthropodsTick Ixodes scapularis