2024
A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria
Chahine Z, Abel S, Hollin T, Barnes G, Chung J, Daub M, Renard I, Choi J, Vydyam P, Pal A, Alba-Argomaniz M, Banks C, Kirkwood J, Saraf A, Camino I, Castaneda P, Cuevas M, De Mercado-Arnanz J, Fernandez-Alvaro E, Garcia-Perez A, Ibarz N, Viera-Morilla S, Prudhomme J, Joyner C, Bei A, Florens L, Ben Mamoun C, Vanderwal C, Le Roch K. A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria. Science 2024, 385: eadm7966. PMID: 39325875, DOI: 10.1126/science.adm7966.Peer-Reviewed Original ResearchConceptsP. falciparum malariaHumanized mouse modelPlasmodium falciparum</i> strainsIn vivo studiesParasite apicoplastDrug sensitivityTherapeutic profileVesicular traffickingGenomic analysisLipid biogenesisSecretory machineryAsexual replicationGenetic analysisReduced susceptibilityCellular traffickingApicoplast functionStrong efficacyMED6Sexual differentiationHemolytic activityDrug pipelineApicoplastKalihinolTraffickingMalariaTafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis
Vydyam P, Pal A, Renard I, Chand M, Kumari V, Gennaro J, Mamoun C. Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis. The Journal Of Infectious Diseases 2024, 229: 161-172. PMID: 38169301, PMCID: PMC10786256, DOI: 10.1093/infdis/jiad315.Peer-Reviewed Original Research
2022
Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti
Chand M, Choi J, Pal A, Singh P, Kumari V, Thekkiniath J, Gagnon J, Timalsina S, Gaur G, Williams S, Ledizet M, Mamoun C. Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti. Frontiers In Cellular And Infection Microbiology 2022, 12: 1039197. PMID: 36506011, PMCID: PMC9732259, DOI: 10.3389/fcimb.2022.1039197.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesAntigen detection assaysMajor immunogenic determinantMost clinical casesReliable biomarkersAntibody combinationsImmunogenic determinantsIntraerythrocytic life cycleClinical casesUnique epitopesBabesia microtiEpitope profilingHuman babesiosisTick-borne diseasesSignificant riseSerological profilingPlasma samplesAntibodiesSerological characterizationProtozoan parasitePublic healthInfectionAntigenDiseaseMammalian hostsBabesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo
Pal AC, Renard I, Singh P, Vydyam P, Chiu JE, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo. The Journal Of Infectious Diseases 2022, 226: 1267-1275. PMID: 35512141, PMCID: PMC10233494, DOI: 10.1093/infdis/jiac181.Peer-Reviewed Original ResearchConceptsLethal infectionC3H/HeJ miceMalaria-like illnessB. duncaniMouse genetic backgroundSurvival outcomesHeJ miceSevere diseaseBabesia duncaniMouse modelDifferent mouse genetic backgroundsDrug susceptibilityBabesia microtiHuman babesiosisIntraerythrocytic parasitesUnique pathogenParasite loadMiceSpecies of BabesiaApicomplexa phylumInfectionBabesia parasitesFree merozoitesHuman erythrocytesGenetic background
2021
Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection
Chiu JE, Renard I, Pal AC, Singh P, Vydyam P, Thekkiniath J, Kumar M, Gihaz S, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection. Antimicrobial Agents And Chemotherapy 2021, 65: 10.1128/aac.00662-21. PMID: 34152821, PMCID: PMC8370247, DOI: 10.1128/aac.00662-21.Peer-Reviewed Original ResearchConceptsEndochin-like quinolonesLethal infectionBlood-borne diseasesBlood-borne pathogensEffective therapyRelated apicomplexan parasitesExperimental therapiesLow doseMouse modelInfectious agentsHuman infectionsInfectionClinical candidatesStrong efficacyB. microtiExcellent safetyMode of actionTherapyErythrocytic developmentAtovaquoneEfficacyApicomplexan parasitesSafetyStructure-activity relationshipsParasitemiaCytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle
Chiu JE, Renard I, George S, Pal A, Alday PH, Narasimhan S, Riscoe MK, Doggett JS, Mamoun C. Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle. The Journal Of Infectious Diseases 2021, 225: 135-145. PMID: 34139755, PMCID: PMC8730496, DOI: 10.1093/infdis/jiab321.Peer-Reviewed Original ResearchConceptsMitochondrial cytochrome bParasite life cycleWild-type alleleTick vectorParasite fitnessCytochrome bMutant parasitesMutant allelesErythrocytic cycleArthropod vectorsNymphal stagesBabesia parasitesMutationsLife cycleFitnessTick stagesResistance mutationsMalaria-like illnessB. microtiAllelesDrug resistance mutationsParasitesHuman babesiosisTicksHost
2020
Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge
Lo MK, Spengler JR, Krumpe LRH, Welch SR, Chattopadhyay A, Harmon JR, Coleman-McCray JD, Scholte FEM, Hotard AL, Fuqua JL, Rose JK, Nichol ST, Palmer KE, O’Keefe B, Spiropoulou CF. Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge. The Journal Of Infectious Diseases 2020, 221: s480-s492. PMID: 32037447, PMCID: PMC7199786, DOI: 10.1093/infdis/jiz630.Peer-Reviewed Original ResearchConceptsSyrian golden hamstersGolden hamstersSevere acute respiratory syndrome coronavirusHuman immunodeficiency virus-1Acute respiratory syndrome coronavirusHepatitis C virusPathogenic zoonotic paramyxovirusImmunodeficiency virus-1Japanese encephalitis virusProphylactic evaluationC virusVirus challengeNiV infectionFatal encephalitisRespiratory diseaseSignificant protectionEncephalitis virusAntiviral activityZoonotic paramyxovirusVirus entrySyncytium formationGreater potencyVirus 1Nipah virusBroad-spectrum activity
2018
A recombinant virus vaccine that protects against both Chikungunya and Zika virus infections
Chattopadhyay A, Aguilar PV, Bopp NE, Yarovinsky TO, Weaver SC, Rose JK. A recombinant virus vaccine that protects against both Chikungunya and Zika virus infections. Vaccine 2018, 36: 3894-3900. PMID: 29807712, DOI: 10.1016/j.vaccine.2018.05.095.Peer-Reviewed Original ResearchConceptsChikungunya virusZika virusA129 miceVesicular stomatitis virusChimeric vesicular stomatitis virusZika virus infectionWild-type miceSingle-dose vaccineRecombinant virus vaccineCo-circulating virusesLicensed vaccineSingle vaccinationZIKV infectionAntibody responsePandemic proportionsVirus vaccineVirus infectionAnimal modelsExperimental vaccinesVaccineMiceInfectionInvasive mosquito vectorsVSV glycoproteinVirus
2017
Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain
van den Pol AN, Mao G, Chattopadhyay A, Rose JK, Davis JN. Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain. Journal Of Virology 2017, 91: 10.1128/jvi.02154-16. PMID: 28077641, PMCID: PMC5331823, DOI: 10.1128/jvi.02154-16.Peer-Reviewed Original ResearchConceptsAdult mouse brainVesicular stomatitis virusVSV glycoprotein (G) geneAdult brainChimeric virusesOncolytic virusesVirus-like vesiclesChimeric vesicular stomatitis virusMouse brainSemliki Forest virusStomatitis virusPostnatal day 14 miceHealthy adult mouse brainRecombinant vesicular stomatitis virusKey immune mechanismsType I interferon responseG glycoproteinI interferon responseInterferon-stimulated genesDay 14 miceInfluenza H5N1 virusGlycoprotein geneNeurotropic natureIntranasal inoculationWild-type vesicular stomatitis virus
2016
Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection
Lauretti F, Chattopadhyay A, de Oliveira França RF, Castro-Jorge L, Rose J, da Fonseca BA. Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection. Human Vaccines & Immunotherapeutics 2016, 12: 2327-2333. PMID: 27185081, PMCID: PMC5027729, DOI: 10.1080/21645515.2016.1183857.Peer-Reviewed Original ResearchConceptsVaccine candidatesBALB/c miceImportant arbovirus diseaseCellular immune responsesDENV-2 infectionDengue-2 virusDENV vaccineHemorrhagic casesVSV virusesSubcutaneous routeHumoral responseC miceClinical trialsLethal infectionImmune responseDENV-2Vaccine vectorControl groupVirus expressionVaccineE expressionMiceFirst inoculationLethal dosesChallenge experiments
2013
Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters
Lo MK, Bird BH, Chattopadhyay A, Drew CP, Martin BE, Coleman JD, Rose JK, Nichol ST, Spiropoulou CF. Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters. Antiviral Research 2013, 101: 26-29. PMID: 24184127, PMCID: PMC3874889, DOI: 10.1016/j.antiviral.2013.10.012.Peer-Reviewed Original ResearchConceptsFatal human encephalitisSingle-dose protectionReplication-defective vesicular stomatitis virusSafety profileLethal challengeSingle doseVirus vaccineEnhanced safety profileHuman encephalitisVaccine vectorVesicular stomatitis virusSyrian hamstersNiV fusionNipah virusBat reservoirsStomatitis virusAttachment glycoproteinHamstersVirusEncephalitisVaccineDose
2012
A Chimeric Vesiculo/Alphavirus Is an Effective Alphavirus Vaccine
Chattopadhyay A, Wang E, Seymour R, Weaver SC, Rose JK. A Chimeric Vesiculo/Alphavirus Is an Effective Alphavirus Vaccine. Journal Of Virology 2012, 87: 395-402. PMID: 23077320, PMCID: PMC3536361, DOI: 10.1128/jvi.01860-12.Peer-Reviewed Original ResearchConceptsChikungunya virusVesicular stomatitis virusChimeric vesicular stomatitis virusAlphavirus vaccinesCellular immune responsesAlphavirus chikungunya virusMosquito-transmitted alphavirusCHIKV glycoproteinsCHIKV infectionCHIKV vaccineLicensed vaccineSingle doseWorldwide epidemicChikungunya feverImmune responseExperimental vaccinesAlphavirus infectionMultiple recent outbreaksVaccineHigh titersChimeric virusesSerious human diseasesVSV glycoproteinVirusRecent outbreak
2010
Complementing Defective Viruses That Express Separate Paramyxovirus Glycoproteins Provide a New Vaccine Vector Approach
Chattopadhyay A, Rose JK. Complementing Defective Viruses That Express Separate Paramyxovirus Glycoproteins Provide a New Vaccine Vector Approach. Journal Of Virology 2010, 85: 2004-2011. PMID: 21177820, PMCID: PMC3067786, DOI: 10.1128/jvi.01852-10.Peer-Reviewed Original Research
2008
Single-dose, virus-vectored vaccine protection against Yersinia pestis challenge: CD4+ cells are required at the time of challenge for optimal protection
Chattopadhyay A, Park S, Delmas G, Suresh R, Senina S, Perlin DS, Rose JK. Single-dose, virus-vectored vaccine protection against Yersinia pestis challenge: CD4+ cells are required at the time of challenge for optimal protection. Vaccine 2008, 26: 6329-6337. PMID: 18832004, PMCID: PMC2628553, DOI: 10.1016/j.vaccine.2008.09.031.Peer-Reviewed Original ResearchConceptsTime of challengeVesicular stomatitis virusVaccine protectionAnti-LcrV antibodySingle-dose protectionDepletion of CD4Recombinant vesicular stomatitis virusYersinia pestis challengeCellular immunityAntibody titersSingle doseIgG1 isotypePlague vaccineLcrV proteinOptimal protectionPlague challengeCD4Stomatitis virusCellsCD8IgG2aVaccineMiceDoseTitersHybrid alphavirus–rhabdovirus propagating replicon particles are versatile and potent vaccine vectors
Rose NF, Publicover J, Chattopadhyay A, Rose JK. Hybrid alphavirus–rhabdovirus propagating replicon particles are versatile and potent vaccine vectors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 5839-5843. PMID: 18391206, PMCID: PMC2311333, DOI: 10.1073/pnas.0800280105.Peer-Reviewed Original ResearchConceptsCellular immune responsesImmune responseVaccine vectorStrong cellular immune responsesPotent vaccine vectorSubsequent lethal challengeInduction of antibodiesSafe vaccine vectorSingle doseLethal challengeReplicon particlesHigh titersPotent inducerVirus-like particlesViral structural proteinsAntibodiesInfectious particlesCell linesVirus glycoproteinRNA repliconsRNA replicationVesicular stomatitis virus glycoproteinVSVAnimal cell linesStructural proteins
2006
An optimized vaccine vector based on recombinant vesicular stomatitis virus gives high-level, long-term protection against Yersinia pestis challenge
Palin A, Chattopadhyay A, Park S, Delmas G, Suresh R, Senina S, Perlin DS, Rose JK. An optimized vaccine vector based on recombinant vesicular stomatitis virus gives high-level, long-term protection against Yersinia pestis challenge. Vaccine 2006, 25: 741-750. PMID: 16959385, DOI: 10.1016/j.vaccine.2006.08.010.Peer-Reviewed Original Research