2023
Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development
Rana V, Kitsou C, Dutta S, Ronzetti M, Zhang M, Bernard Q, Smith A, Tomás-Cortázar J, Yang X, Wu M, Kepple O, Li W, Dwyer J, Matias J, Baljinnyam B, Oliver J, Rajeevan N, Pedra J, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, Pal U. Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development. Science 2023, 379: eabl3837. PMID: 36634189, PMCID: PMC10122270, DOI: 10.1126/science.abl3837.Peer-Reviewed Original ResearchConceptsBlood meal acquisitionMetazoan developmentTick receptorArthropod immunityMammalian hostsSignaling pathwaysReceptor motifEvolutionary dependenceVectorial competenceStem cellsCommunication pathwaysPathwayCritical roleVector immunityHostHigh affinityGenomeAntimicrobial componentsHedgehogJAKMotifMetamorphosisImmunityParasitesPhysiology
2021
Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies
Matias J, Kurokawa C, Sajid A, Narasimhan S, Arora G, Diktas H, Lynn GE, DePonte K, Pardi N, Valenzuela JG, Weissman D, Fikrig E. Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies. Vaccine 2021, 39: 7661-7668. PMID: 34862075, PMCID: PMC8671329, DOI: 10.1016/j.vaccine.2021.11.003.Peer-Reviewed Original ResearchConceptsTick bite siteTick immunityAntigen deliveryBite siteGuinea pigsDevelopment of vaccinesIxodes scapularis ticksProtein immunizationAntibody responseTick biteVaccine platformLipid nanoparticlesMRNA lipid nanoparticlesMRNA-LNPModel antigenTick salivaEarly hallmarkImmunityTick-borne diseasesScapularis ticksTick challengeErythemaSalivary componentsFactor XaDelivery strategiesA Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice
Chuang YM, Tang XD, Fikrig E. A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice. Infection And Immunity 2021, 90: e00359-21. PMID: 34724388, PMCID: PMC8788779, DOI: 10.1128/iai.00359-21.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesFuture malaria vaccinesInfection of miceIsotype monoclonal antibodyVector antigensProtective immunityPassive immunizationMalaria vaccinePlasmodium infectionPassive transferProtein monoclonal antibodySignificant protectionSynergistic protectionMiceInfectionAntibodiesFc regionAntiserumVertebrate hostsProtein TrioImmunizationVaccineMalariaAntigenImmunityProbing 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
2020
Fractionation of tick saliva reveals proteins associated with the development of acquired resistance to Ixodes scapularis
Černý J, Lynn G, DePonte K, Ledizet M, Narasimhan S, Fikrig E. Fractionation of tick saliva reveals proteins associated with the development of acquired resistance to Ixodes scapularis. Vaccine 2020, 38: 8121-8129. PMID: 33168347, DOI: 10.1016/j.vaccine.2020.10.087.Peer-Reviewed Original ResearchConceptsTick-borne pathogensTick immunityTick salivaTick vaccinesMultiple tick-borne pathogensIxodes scapularisGuinea pig modelTick salivary antigensTick rejectionTick Ixodes scapularisPig modelTick feedingNortheast USASalivary antigensGlobal medical problemDevelopment of vaccinesTicksMain vectorPathogensSaliva fractionsScapularisMedical problemsImmunityVaccineSaliva
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
2018
Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance
Shaw DK, Tate AT, Schneider DS, Levashina EA, Kagan JC, Pal U, Fikrig E, Pedra JHF. Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance. Trends In Immunology 2018, 39: 862-873. PMID: 30301592, PMCID: PMC6218297, DOI: 10.1016/j.it.2018.09.003.Peer-Reviewed Original ResearchConceptsVector immunityEvolutionary ecologyEvolutionary forcesEvolutionary ecologistsGenetic plasticityVector-borne pathogensArthropod populationsAbiotic factorsMolecular immunologistsMicrobial assaultImmune systemInnate defenseRecent scientific breakthroughsEcologyEcologistsImmune responsePathogenicityImmunityPathogensPlasticityDefenseToleranceResistanceScientific breakthroughsSmall Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus
Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee SK, Kumar P. Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus. Cell Host & Microbe 2018, 23: 549-556.e3. PMID: 29606496, PMCID: PMC6074029, DOI: 10.1016/j.chom.2018.03.001.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionCell-mediated immune responsesLate-stage therapySubsequent WNV infectionWNV-infected miceLong-term immunityNile virusWNV E proteinViral burdenIntranasal routeVirus clearanceVirus infectionImmune responseMice succumbPeripheral tissuesNatural immunitySurvival rateDisease resultsDay 9Virus replicationInfectionImmunityCNSVirus
2016
TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice
Paul AM, Acharya D, Le L, Wang P, Stokic DS, Leis AA, Alexopoulou L, Town T, Flavell RA, Fikrig E, Bai F. TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice. The Journal Of Immunology 2016, 197: 4425-4435. PMID: 27798161, PMCID: PMC5123688, DOI: 10.4049/jimmunol.1600902.Peer-Reviewed Original ResearchConceptsWest Nile virusAntiviral immunityWNV infectionWest Nile virus infectionOverexpression of TLR7Induced IFNsWild-type controlsSuppressor of cytokineTLR7 expressionNeuronal deathVirus infectionHuman TLR7TLR7TLR8InfectionMiceX proteinReduced expressionImmunityNile virusSOCS-1RNA knockdownIFNNovel roleProapoptotic genes
2011
Identification 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 ResearchConceptsSalivary 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
2009
Human innate immunosenescence: causes and consequences for immunity in old age
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC. Human innate immunosenescence: causes and consequences for immunity in old age. Trends In Immunology 2009, 30: 325-333. PMID: 19541535, PMCID: PMC4067971, DOI: 10.1016/j.it.2009.05.004.Peer-Reviewed Original ResearchConceptsInnate immune system initiatesNatural killer T cellsOlder ageAntiviral cytokine productionKiller T cellsInnate immune responseInnate immune systemDendritic cellsNatural killerCytokine productionHuman immunosenescenceT cellsImmune responseAdaptive immunityImmune systemInnate immunityImmunityAgeCellsDiverse cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfection
2007
Immunity against Ixodes scapularis Salivary Proteins Expressed within 24 Hours of Attachment Thwarts Tick Feeding and Impairs Borrelia Transmission
Narasimhan S, DePonte K, Marcantonio N, Liang X, Royce TE, Nelson KF, Booth CJ, Koski B, Anderson JF, Kantor F, Fikrig E. Immunity against Ixodes scapularis Salivary Proteins Expressed within 24 Hours of Attachment Thwarts Tick Feeding and Impairs Borrelia Transmission. PLOS ONE 2007, 2: e451. PMID: 17505544, PMCID: PMC1866177, DOI: 10.1371/journal.pone.0000451.Peer-Reviewed Original Research
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
Invasion and survival strategies of Anaplasma phagocytophilum
Carlyon JA, Fikrig E. Invasion and survival strategies of Anaplasma phagocytophilum. Cellular Microbiology 2003, 5: 743-754. PMID: 14531890, DOI: 10.1046/j.1462-5822.2003.00323.x.Peer-Reviewed Original ResearchConceptsAnaplasma phagocytophilumA. phagocytophilumHuman granulocytic ehrlichiosisHostile intracellular environmentTick-borne zoonosisObligate intracellular bacteriumHost neutrophilsNeutrophil adhesionInnate immunityPolymorphonuclear leucocytesAetiological agentGranulocytic ehrlichiosisIntracellular bacteriumNeutrophilsMicrobicidal activityPhagocytophilumHost cellsProteolytic compoundsAcidic lysosomesBacteria-containing phagosomesKey playersLeucocytesImmunityEhrlichiosisPhagocytes
2001
West Nile Virus Envelope Protein
WANG T, ANDERSON J, MAGNARELLI L, BUSHMICH S, WONG S, KOSKI R, FIKRIG E. West Nile Virus Envelope Protein. Annals Of The New York Academy Of Sciences 2001, 951: 325-327. PMID: 11797789, DOI: 10.1111/j.1749-6632.2001.tb02708.x.Peer-Reviewed Original ResearchConceptsWest Nile virus envelope proteinVirus envelope proteinWest Nile virus infectionRole of antibodiesE proteinEnvelope proteinWest Nile virusPassive immunizationHumoral responseWest Nile virus E proteinVirus infectionVirus E proteinNile virusProtein serumInfectionAntibodiesRecombinant formPatientsImmunizationProteinMiceDiagnosisImmunitySerum
1998
Prevention of Borrelia burgdorferi transmission in guinea pigs by tick immunity.
Nazario S, Das S, de Silva AM, Deponte K, Marcantonio N, Anderson JF, Fish D, Fikrig E, Kantor FS. Prevention of Borrelia burgdorferi transmission in guinea pigs by tick immunity. American Journal Of Tropical Medicine And Hygiene 1998, 58: 780-5. PMID: 9660463, DOI: 10.4269/ajtmh.1998.58.780.Peer-Reviewed Original ResearchGranulocytic Ehrlichiosis in Tick-Immune Guinea Pigs
Das S, Deponte K, Marcantonio N, Ijdo J, Hodzic E, Katavolos P, Barthold S, Telford S, Kantor F, Fikrig E. Granulocytic Ehrlichiosis in Tick-Immune Guinea Pigs. Infection And Immunity 1998, 66: 1803-1805. PMID: 9529119, PMCID: PMC108126, DOI: 10.1128/iai.66.4.1803-1805.1998.Peer-Reviewed Original Research
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 diseasesAgentsNeutropeniaImmunizationInfectionLeukocytesDiseaseAntibodiesAblation of interleukin-12 exacerbates Lyme arthritis in SCID mice
Anguita J, Samanta S, Barthold SW, Fikrig E. Ablation of interleukin-12 exacerbates Lyme arthritis in SCID mice. Infection And Immunity 1997, 65: 4334-4336. PMID: 9317045, PMCID: PMC175621, DOI: 10.1128/iai.65.10.4334-4336.1997.Peer-Reviewed Original ResearchBorrelia burgdorferi P35 and P37 Proteins, Expressed In Vivo, Elicit Protective Immunity
Fikrig E, Barthold S, Sun W, Feng W, Telford S, Flavell R. Borrelia burgdorferi P35 and P37 Proteins, Expressed In Vivo, Elicit Protective Immunity. Immunity 1997, 6: 531-539. PMID: 9175831, DOI: 10.1016/s1074-7613(00)80341-6.Peer-Reviewed Original ResearchConceptsElicit protective immunityB. burgdorferiIgG titersProtective immunityInfected miceImmune responseHost immunityLyme borreliosisRT-PCR analysisMiceVivo-expressed antigensBorrelia burgdorferi genesImmunityP35BurgdorferiP37 proteinVivoNorthern blotAntiserumP37PatientsAntigenELISATitersBorreliosis