2024
Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites
Lapidus S, Goheen M, Sy M, Deme A, Ndiaye I, Diedhiou Y, Mbaye A, Hagadorn K, Sene S, Pouye M, Thiam L, Ba A, Guerra N, Mbengue A, Raduwan H, Gagnon J, Vigan-Womas I, Parikh S, Ko A, Ndiaye D, Fikrig E, Chuang Y, Bei A. Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites. The Journal Of Infectious Diseases 2024, jiae525. PMID: 39475423, DOI: 10.1093/infdis/jiae525.Peer-Reviewed Original ResearchModerate transmission areasMosquito salivary proteinsModerately endemic areaAntibody responseMosquito exposureTransmission seasonP. falciparum infectionMalaria transmission seasonMalaria transmission intensityExposure to infectious mosquitoesMosquito bitesEntomological inoculation rateEndemic areasHuman immune responseInfected mosquito bitesTransmission areasDecline 3 monthsNo antibody responseExposure to infected mosquitoesP. falciparumControl cohortExposure to mosquitoesBead-based assayImmune responseSalivary proteinsSalp14 epitope-based mRNA vaccination induces early recognition of a tick bite
Cui Y, Cibichakravarthy B, Tang X, Alameh M, Dwivedi G, Weissman D, Fikrig E. Salp14 epitope-based mRNA vaccination induces early recognition of a tick bite. Vaccine 2024, 42: 126304. PMID: 39236403, PMCID: PMC11416896, DOI: 10.1016/j.vaccine.2024.126304.Peer-Reviewed Original ResearchTick bite siteGuinea pigsMRNA-LNPMRNA vaccinesBite siteImmunized guinea pigsTiters of IgGIxodes scapularis ticksDevelopment of erythemaLipid nanoparticlesSkin of guinea pigsI. scapularisTicksErythemaHistamine activityPigsTick bitesCarboxyl terminusRepeated exposureExposure of animalsAmino acidsSalivary proteinsVaccineMRNAGuineaThe human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872. PMID: 39121194, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2023
Malaria: influence of Anopheles mosquito saliva on Plasmodium infection
Arora G, Chuang Y, Sinnis P, Dimopoulos G, Fikrig E. Malaria: influence of Anopheles mosquito saliva on Plasmodium infection. Trends In Immunology 2023, 44: 256-265. PMID: 36964020, PMCID: PMC10074230, DOI: 10.1016/j.it.2023.02.005.Peer-Reviewed Original ResearchConceptsAnopheles salivaPlasmodium infectionInfected female mosquitoesMosquito salivary proteinsLocal host responseComponents of salivaMosquito salivaTherapeutic strategiesHost responsePlasmodium sporozoitesVector salivaPlasmodium protozoaBlood vesselsSalivaFemale mosquitoesBlood mealAnopheline mosquitoesInfectionMalariaVector-borne diseasesSkinHost-pathogen interactionsSporozoitesSalivary proteinsMosquitoesMosquito Salivary Proteins and Arbovirus Infection: From Viral Enhancers to Potential Targets for Vaccines
Marín-López A, Raduwan H, Chen T, Utrilla-Trigo S, Wolfhard D, Fikrig E. Mosquito Salivary Proteins and Arbovirus Infection: From Viral Enhancers to Potential Targets for Vaccines. Pathogens 2023, 12: 371. PMID: 36986293, PMCID: PMC10054260, DOI: 10.3390/pathogens12030371.Peer-Reviewed Original ResearchMosquito salivary proteinsImmune responseImportant public health challengeAdaptive immune responsesHost immune responsePublic health challengeNon-endemic areasSalivary proteinsSerious complicationsLicensed vaccineNeurological alterationsMosquito salivaClinical signsMosquito bitesHemorrhagic feverInfection outcomesRapid onsetArbovirus infectionExplosive outbreaksHealth challengesVaccineDifferent arbovirusesArboviral diseasesArthropod salivaPotential target
2022
Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia
Olajiga O, Marin-Lopez A, Cardenas J, Gutierrez-Silva L, Gonzales-Pabon M, Maldonado-Ruiz L, Worges M, Fikrig E, Park Y, Londono-Renteria B. Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia. Frontiers In Epidemiology 2022, 2: 1002857. PMID: 38455331, PMCID: PMC10910902, DOI: 10.3389/fepid.2022.1002857.Peer-Reviewed Original ResearchIgG antibodiesDengue virusZika virusWest Nile virus infectionDengue disease progressionSystemic immune responsesPotential protective effectFever endemic areasDengue-endemic regionsSalivary proteinsProduction of antibodiesFemale Aedes mosquitoesSalivary gland extractsNterm-34Clinical characteristicsIgG levelsDENV infectionAntibody responseDisease progressionArboviral infectionsVirus infectionImmune responseMosquito bitesProtective effectImmunomodulatory properties
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
The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells
Chuang YM, Agunbiade TA, Tang XD, Freudzon M, Almeras L, Fikrig E. The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells. The Journal Of Infectious Diseases 2020, 224: 544-553. PMID: 33306099, PMCID: PMC8328219, DOI: 10.1093/infdis/jiaa759.Peer-Reviewed Original ResearchConceptsPassive immunizationCell traversal activityMosquito saliva proteinsMosquito salivary proteinsMosquito salivaNeutrophil chemotaxisProtein monoclonal antibodyProtective effectSporozoite glidingSporozoite infectivitySporozoite traversalMonoclonal antibodiesHost skinAnopheles mosquitoesProtein 1ImmunizationBlood mealSporozoitesSalivaMiceHost cellsSaliva proteinsSalivary proteinsAntiserumVertebrate hostsVaccination with Aedes aegypti AgBR1 Delays Lethal Mosquito-Borne Zika Virus Infection in Mice
Wang Y, Marin-Lopez A, Jiang J, Ledizet M, Fikrig E. Vaccination with Aedes aegypti AgBR1 Delays Lethal Mosquito-Borne Zika Virus Infection in Mice. Vaccines 2020, 8: 145. PMID: 32218189, PMCID: PMC7348886, DOI: 10.3390/vaccines8020145.Peer-Reviewed Original ResearchZika virusZIKV infectionGuillain-Barre syndromeMosquito salivary proteinsZika virus infectionNeurological complicationsAcute illnessFetal microcephalyPassive immunizationActive immunizationAsymptomatic infectionInflammatory responseAedes aegypti mosquitoesVirus infectionBite siteInfectionAegypti mosquitoesImmunizationMiceSalivary proteinsAgBR1MosquitoesComplicationsHeadacheVaccination
2019
Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice
Chuang YM, Freudzon M, Yang J, Dong Y, Dimopoulos G, Fikrig E. Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice. Infection And Immunity 2019, 87: 10.1128/iai.00326-19. PMID: 31285253, PMCID: PMC6704594, DOI: 10.1128/iai.00326-19.Peer-Reviewed Original ResearchConceptsBite siteControl mosquitoesMosquito salivary proteinsInfectivity of sporozoitesMosquito salivary glandsProinflammation cytokinesSporozoite infectionRNA interference-mediated silencingPlasmodium bergheiMiceSalivary glandsSporozoitesTNFExpression of genesMosquitoesSalivary proteinsBurdenExpressionVertebrate hostsSplenocytesCytokinesInfectionCell adhesionLiverBergheiAgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice
Uraki R, Hastings AK, Brackney DE, Armstrong PM, Fikrig E. AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice. Npj Vaccines 2019, 4: 23. PMID: 31312526, PMCID: PMC6614468, DOI: 10.1038/s41541-019-0120-x.Peer-Reviewed Original ResearchWest Nile virus infectionWest Nile virusVirus infectionInfected Aedes aegypti mosquitoesZika virus pathogenesisMosquito salivary proteinsViral loadAedes aegypti mosquitoesLethal infectionVirus pathogenesisSevere diseaseInfectionNile virusAegypti mosquitoesMiceAntibodiesSalivary proteinsMosquitoesMeningoencephalitisPathogenesisAgBR1DiseaseAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
2017
Chapter 14 Translation of Saliva Proteins Into Tools to Prevent Vector-Borne Disease Transmission
Narasimhan S, Schleicher T, Fikrig E. Chapter 14 Translation of Saliva Proteins Into Tools to Prevent Vector-Borne Disease Transmission. 2017, 249-300. DOI: 10.1016/b978-0-12-805360-7.00014-9.ChaptersPathogen transmissionArthropod vectorsVector-pathogen interactionsBlood mealVector salivaVector-Borne Disease TransmissionTransmit pathogensMolecular understandingHematophagous arthropodsHost immune responseMicrobesArthropodsImmune responseSalivary proteinsPathogensHostArthropod salivaMicroorganism transmission
2012
Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a murine model of Lyme borreliosis
Ullmann AJ, Dolan MC, Sackal CA, Fikrig E, Piesman J, Zeidner NS. Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a murine model of Lyme borreliosis. Ticks And Tick-borne Diseases 2012, 4: 160-163. PMID: 23141105, PMCID: PMC4306421, DOI: 10.1016/j.ttbdis.2012.08.006.Peer-Reviewed Original ResearchConceptsTick salivary proteinsBorrelia burgdorferi infectionSalivary proteinsTick salivary gland proteinsSalivary gland proteinsTh1 responseImmunized miceSpecific immunityBurgdorferi infectionMurine modelSpirochete loadLyme borreliosisPrior exposureAdenovirus expression systemAdenoviral vectorTick challengeVaccinationMammalian hostsIxodes scapularisVertebrate hosts
2011
A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent
Schuijt TJ, Coumou J, Narasimhan S, Dai J, DePonte K, Wouters D, Brouwer M, Oei A, Roelofs JJ, van Dam AP, van der Poll T, Veer C, Hovius JW, Fikrig E. A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent. Cell Host & Microbe 2011, 10: 136-146. PMID: 21843870, PMCID: PMC3170916, DOI: 10.1016/j.chom.2011.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBorrelia burgdorferiCell Migration AssaysCloning, MolecularComplement Membrane Attack ComplexComplement Pathway, Mannose-Binding LectinFemaleGene SilencingHemolysisHumansImmunization, PassiveImmunotherapy, ActiveInsect ProteinsIxodesLarvaLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataNeutrophilsNymphPhagocytosisRabbitsRecombinant ProteinsSalivaSalivary Proteins and PeptidesSequence AlignmentConceptsComplement cascadeLyme disease agent Borrelia burgdorferiImpaired neutrophil phagocytosisTick salivary proteinsVector-borne pathogensLyme disease agentMammalian infectionVector colonizationVertebrate hostsTick midgutAlternative complement pathwayBorrelia transmissionComplement-mediated killingVector proteinNeutrophil phagocytosisEssential rolePathway inhibitorComplement pathwayDisease agentsSalivary proteinsBorrelia burgdorferiLectin inhibitorsProteinCascadeIxodes ticks
2010
Immunization with Adenoviral-expressed salivary gland proteins (SALPs) decreases spirochete load in a murine model of Lyme borreliosis (52.2)
Ullmann A, Dolan M, Fikrig E, Piesman J, Zeidner N. Immunization with Adenoviral-expressed salivary gland proteins (SALPs) decreases spirochete load in a murine model of Lyme borreliosis (52.2). The Journal Of Immunology 2010, 184: 52.2-52.2. DOI: 10.4049/jimmunol.184.supp.52.2.Peer-Reviewed Original ResearchBurgdorferi infectionMurine modelTick salivary proteinsC3H/HeJ miceDendritic cell expressionCellular immune responsesBorrelia burgdorferi infectionB. burgdorferi infectionLeast partial protectionSalivary proteinsSalivary gland proteinsImmunized miceSpecific immunitySpirochete burdenImmunomodulatory factorsHeJ miceVaccination techniqueImmune responseI. scapularis ticksTarget organsProtein antibodiesCell expressionSpirochete loadTick salivaLyme borreliosis
2009
Inhibition 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
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
2006
Cutting Edge: CD4 Is the Receptor for the Tick Saliva Immunosuppressor, Salp15
Garg R, Juncadella IJ, Ramamoorthi N, Ashish, Ananthanarayanan SK, Thomas V, Rincón M, Krueger JK, Fikrig E, Yengo CM, Anguita J. Cutting Edge: CD4 Is the Receptor for the Tick Saliva Immunosuppressor, Salp15. The Journal Of Immunology 2006, 177: 6579-6583. PMID: 17082567, PMCID: PMC4302324, DOI: 10.4049/jimmunol.177.10.6579.Peer-Reviewed Original ResearchConceptsDownstream effector proteinsSrc kinase LckC-terminal residuesLipid raft reorganizationEffector proteinsKinase LckTyrosine phosphorylationMolecular basisExtracellular domainEarly stepsSalp15T cell activationSalivary proteinsCD4 coreceptorProteinCalcium fluxCell activationT cellsCellsLckRepressionPhosphorylationIL-2 productionResiduesCoreceptorAn Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands
Sukumaran B, Narasimhan S, Anderson JF, DePonte K, Marcantonio N, Krishnan MN, Fish D, Telford SR, Kantor FS, Fikrig E. An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands. Journal Of Experimental Medicine 2006, 203: 1507-1517. PMID: 16717118, PMCID: PMC2118316, DOI: 10.1084/jem.20060208.Peer-Reviewed Original ResearchConceptsA. phagocytophilum-infected miceRNA interference-mediated silencingA. phagocytophilumTick salivary proteinsI. scapularis salivary glandsRickettsia-like pathogensTick salivary glandsMammalian hostsGenus RickettsiaAnaplasma phagocytophilumGene expressionSalivary glandsIntracellular organismsArthropodsSalivary proteinsPathogensProteinPhagocytophilumExpressionTicksHuman anaplasmosisSilencingGenesOrganismsAnaplasma