2025
Altering the intracellular trafficking of Necator americanus GST-1 antigen yields novel hookworm mRNA vaccine candidates
De Oliveira A, Versteeg L, Briggs N, Adhikari R, Villar M, Redd J, Hotez P, Bottazzi M, Pollet J. Altering the intracellular trafficking of Necator americanus GST-1 antigen yields novel hookworm mRNA vaccine candidates. PLOS Neglected Tropical Diseases 2025, 19: e0012809. PMID: 39792959, PMCID: PMC11756802, DOI: 10.1371/journal.pntd.0012809.Peer-Reviewed Original ResearchConceptsAntigen-specific antibodiesMRNA vaccine candidateMRNA vaccinesVaccine candidatesNa-GST-1Plasma membrane-anchoredRobust CD8+ T-cell responsesCD8+ T cell responsesMemory T cell populationsTiters of antigen-specific antibodiesLevels of antigen-specific antibodiesT cell responsesT cell populationsRecombinant Na-GST-1In vivo efficacySubunit vaccine candidateInduce humoral responsesImmunogenicity findingsNeutralizing antibodiesClinical studiesDevelopment of multivalent vaccinesHumoral responseRNA vaccinesImmune responsePeptide presentation
2024
Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs
Lewis C, Xie L, Bhandarkar S, Jin D, Abdallah K, Draycott A, Chen Y, Thoreen C, Gilbert W. Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs. Molecular Cell 2024, 85: 445-459.e5. PMID: 39706187, PMCID: PMC11780321, DOI: 10.1016/j.molcel.2024.11.030.Peer-Reviewed Original ResearchConceptsTranslation initiationUntranslated regionHuman 5'-untranslated regionChemically modified nucleotidesHigh-throughput methodRibosome recruitmentAlternative isoformsRegulatory elementsEnhanced translationDissecting mechanismsTherapeutic mRNANucleotideTherapeutic proteinsMRNADelivery of therapeutic proteinsSequenceMRNA vaccinesEndogenous RNAQuantitative profilingWidespread effectsTranslation outputRNATherapeuticsIsoformsCellular immunogenicitymRNA Vaccines Against Tick‐borne Diseases
Arora G, Fikrig E. mRNA Vaccines Against Tick‐borne Diseases. 2024, 285-301. DOI: 10.1002/9783527838394.ch10.Peer-Reviewed Original ResearchTick-borne diseasesMRNA vaccinesIxodes scapularis ticksCrimean-Congo hemorrhagic feverEffective memory responsesVector-borne diseasesIncreasing cost of developmentPowassan virusModified mRNA vaccineMRNA-based vaccinesTicksVaccine platformTurnover timeLipid nanoparticlesMemory responsesClinical trialsImmune systemEffective vaccineMultiple antigensPathogensSpreading virusArthropodsVaccineDiseaseHemorrhagic feverA substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity
Li Y, Zhang X, Tai W, Zhuang X, Shi H, Liao S, Yu X, Mei R, Chen X, Huang Y, Liu Y, Liu J, Liu Y, Zhu Y, Wang P, Tian M, Yu G, Li L, Cheng G. A substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity. EBioMedicine 2024, 110: 105437. PMID: 39531918, PMCID: PMC11603013, DOI: 10.1016/j.ebiom.2024.105437.Peer-Reviewed Original ResearchS proteinCytoplasmic tailFERM-binding motifTrans-complementation systemSpike proteinAmino acid substitutionsProline-to-leucine substitutionSystematic bioinformatics analysisHigh-frequency mutationsSARS-CoV-2 virionsBinding motifAcid substitutionsSARS-CoV-2Natural selectionBioinformatics analysisEzrin/radixin/moesin proteinsMolecular mechanismsMutationsOmicron variantProteinVaccine developmentMRNA vaccinesGlobal disseminationSARS-CoV-2 Omicron sublineagesSublineagesImmunogenicity and Efficacy of Personalized Adjuvant mRNA Cancer Vaccines.
Berraondo P, Cuesta R, Sanmamed M, Melero I. Immunogenicity and Efficacy of Personalized Adjuvant mRNA Cancer Vaccines. Cancer Discovery 2024, 14: 2021-2024. PMID: 39485256, DOI: 10.1158/2159-8290.cd-24-1196.Peer-Reviewed Original ResearchSalp14 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 proteinsVaccineMRNAGuineaDeciphering the HLA-E immunopeptidome with mass spectrometry: an opportunity for universal mRNA vaccines and T-cell-directed immunotherapies
Weitzen M, Shahbazy M, Kapoor S, Caron E. Deciphering the HLA-E immunopeptidome with mass spectrometry: an opportunity for universal mRNA vaccines and T-cell-directed immunotherapies. Frontiers In Immunology 2024, 15: 1442783. PMID: 39301027, PMCID: PMC11410602, DOI: 10.3389/fimmu.2024.1442783.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMass spectrometryHLA-EHLA moleculesT-cell-directed immunotherapyCD8+ T cellsNovel cell surface antigensNon-classical HLA-EHLA-E moleculesCell surface antigensPeptides to CD8T cellsMRNA vaccinesTherapeutic efficacySurface antigensImmunotherapyMoleculesSpectrometryTherapeutic targetImmunopeptidomePathogen-derivedCD8Peptide repertoirePeptide fragmentsHLAMinimal polymorphismEffectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study
Neto F, Hitchings M, Amin A, de França G, Lind M, Torres M, Tsuha D, de Oliveira R, Cummings D, Dean N, Andrews J, Ko A, Croda J, Ranzani O. Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study. The Lancet Regional Health - Americas 2024, 34: 100755. PMID: 38737773, PMCID: PMC11087726, DOI: 10.1016/j.lana.2024.100755.Peer-Reviewed Original ResearchSevere COVID-19Cohort ACohort B.Cohort BTwo-doseMRNA vaccinesPrimary outcomeBooster dose effectivenessCOVID-19 outcomesPopulation-based cohort studyDose of COVID-19 vaccinePopulation-based cohortPopulation-based cohort of individualsCOVID-19 vaccine dosesSevere COVID-19 outcomesFollow-upCohort studyMRNA-basedVaccine doseCohort of individualsVaccine effectivenessVaccine combinationsDoseLower hazardCohortIL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, Jeon S, You S, Racke M, Bucala R, Kang I. IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination. EBioMedicine 2024, 103: 105114. PMID: 38640835, PMCID: PMC11041015, DOI: 10.1016/j.ebiom.2024.105114.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsCOVID-19 mRNA vaccinesAntigen-specific CD4<sup>+</sup> T cell responsesT cell responsesPrimary antibody deficiencyCD4<sup>+</sup> T cell responsesT cellsIL-1R1MRNA vaccinesIL-1IgG antibodiesAntigen-specific CD4<sup>+</sup> T cellsCD4+ T cell responsesLevels of IL-1R1Human CD4<sup>+</sup> T cellsIL-1 receptor 1Healthy individualsDose of COVID-19 mRNA vaccineAntigen-specific CD4IL-1R1 expressionT cell immunityRepetitive antigenic stimulationCytokines interleukin (IL)-1Immune response to virusesExpression of IL-1R1Reactive axillary lymph nodes after COVID-19 mRNA vaccination: comparison of mRNA vs. attenuated whole-virus vaccines
Adin M, Isufi E, Wu J, Pang Y, Nguyen D, Has D, Caner C, Aboueldaha N, Mossa-Basha M, Pucar D. Reactive axillary lymph nodes after COVID-19 mRNA vaccination: comparison of mRNA vs. attenuated whole-virus vaccines. Nuclear Medicine Communications 2024, 45: 474-480. PMID: 38465449, DOI: 10.1097/mnm.0000000000001833.Peer-Reviewed Original ResearchAxillary lymph nodesWhole virus vaccineLymph nodesMRNA vaccinesNatural courseValue of clinical parametersCOVID-19 mRNA vaccinesPredictive value of clinical parametersDose of vaccine administrationPET-CT studiesCohort of oncology patientsDeauville criteriaPET criteriaClinical parametersYounger patientsSingle doseModerna recipientsJ&J vaccinePET-positiveMultivariate analysisVaccine typesOncology patientsPredictive valueVaccine administrationModerna vaccineLow antibody levels associated with significantly increased rate of SARS‐CoV‐2 infection in a highly vaccinated population from the US National Basketball Association
Tai C, Haviland M, Kissler S, Lucia R, Merson M, Maragakis L, Ho D, Anderson D, DiFiori J, Grubaugh N, Grad Y, Mack C. Low antibody levels associated with significantly increased rate of SARS‐CoV‐2 infection in a highly vaccinated population from the US National Basketball Association. Journal Of Medical Virology 2024, 96: e29505. PMID: 38465748, DOI: 10.1002/jmv.29505.Peer-Reviewed Original ResearchConceptsAntibody levelsSARS-CoV-2 infectionSARS-CoV-2 antibody levelsPfizer-BioNTech mRNA vaccineHistory of SARS-CoV-2 infectionCox proportional hazards modelsLow antibody levelsProportional hazards modelRisk of infectionMRNA vaccinesRates of SARS-CoV-2 infectionAnalytic cohortPrimary seriesPfizer-BioNTechVaccine doseIncreased rate of SARS-CoV-2 infectionInterquartile rangeBooster schedulesHazards modelSerological testsInfectionSARS-CoV-2Vaccinated individualsAntibodiesAntibody test
2023
Sensitizing the Efficiency of ICIs by Neoantigen mRNA Vaccines for HCC Treatment
Han R, Wang Y, Lu L. Sensitizing the Efficiency of ICIs by Neoantigen mRNA Vaccines for HCC Treatment. Pharmaceutics 2023, 16: 59. PMID: 38258070, PMCID: PMC10821464, DOI: 10.3390/pharmaceutics16010059.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsMRNA vaccinesCheckpoint inhibitorsHCC treatmentEffectiveness of mRNAMRNA cancer vaccinesNovel mRNA vaccineSuppressive tumor microenvironmentHepatocellular carcinoma patientsCancer-associated antigensInnovative therapeutic strategiesCOVID-19 preventionCarcinoma patientsVaccine delivery vehiclesCancer vaccinesClinical evidenceHCC preventionTherapeutic strategiesVaccineTumor microenvironmentCancer treatmentPotential targetNew hopeTreatmentTrials2368. SARS-CoV-2 mRNA vaccination induces B cell immunity in the tonsils and adenoids of children
Xu Q, Mudd P, Behzadpour H, Bellusci L, Grubbs G, Pourhashemi S, Tang J, Liu C, Newman D, Shi L, Milanez-Almeida P, Kardava L, Tsang J, Moir S, Khurana S, Schwartzberg P, Manthiram K. 2368. SARS-CoV-2 mRNA vaccination induces B cell immunity in the tonsils and adenoids of children. Open Forum Infectious Diseases 2023, 10: ofad500.1989. PMCID: PMC10677082, DOI: 10.1093/ofid/ofad500.1989.Peer-Reviewed Original ResearchSARS-CoV-2-specific B cellsMemory B cellsB cellsAdenoids of childrenMRNA vaccinesVaccinated subjectsPeripheral bloodInfected subjectsUpper respiratory tract lymphoid tissueSARS-CoV-2IgA+ memory B cellsSARS-CoV-2 mRNA vaccinesGerminal center B cellsRobust adaptive immune responsesPost-vaccinationCOVID-19 mRNA vaccinesB-cell phenotypeB cell immunityAdaptive immune responsesImmunity to SARS-CoV-2SARS-CoV-2 infectionPost-infectionLymphoid tissueAdenoidsMucosal IgAComparative Effectiveness of Bivalent (Original/Omicron BA.4/BA.5) COVID-19 Vaccines in Adults
Kopel H, Nguyen V, Boileau C, Bogdanov A, Winer I, Ducruet T, Zeng N, Bonafede M, Esposito D, Martin D, Rosen A, Van de Velde N, Vermund S, Gravenstein S, Mansi J. Comparative Effectiveness of Bivalent (Original/Omicron BA.4/BA.5) COVID-19 Vaccines in Adults. Vaccines 2023, 11: 1711. PMID: 38006043, PMCID: PMC10675676, DOI: 10.3390/vaccines11111711.Peer-Reviewed Original ResearchCOVID-19-related hospitalizationRelative vaccine effectivenessOutpatient visitsPrimary care electronic health recordsCOVID-19-related outcomesVaccine-induced protectionMedical claims dataCOVID-19 vaccineSARS-CoV-2Electronic health recordsVaccine effectivenessVaccine recipientsMRNA vaccinesBivalent vaccineBaseline differencesStudy populationClaims dataOmicron variantComparative effectivenessHospitalizationPropensity scoreVaccineOlder adultsHealth recordsVisitsIncidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice
Ali M, Johnson M, Irwin T, Henry S, Sugeng L, Kansal S, Allison T, Bremer M, Jones V, Martineau M, Wong C, Marecki G, Stebbins J, Michelena H, McCully R, Svatikova A, Padang R, Scott C, Kanuga M, Arsanjani R, Pellikka P, Kane G, Thaden J. Incidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice. Journal Of The American Society Of Echocardiography 2023, 37: 276-284.e3. PMID: 37879379, DOI: 10.1016/j.echo.2023.10.010.Peer-Reviewed Original ResearchConceptsUltrasound enhancing agentsAdverse drug reactionsSevere adverse drug reactionsDrug reactionsEchocardiography databaseHealth systemFrequency of severe adverse drug reactionsIsolated back painUS health systemST-segment elevationIncidence of severe adverse drug reactionsLoss of pulseCardiopulmonary involvementLoss of consciousnessMRNA vaccinesLumasonMatched controlsRare riskEnhancing agentsADR rateProspective reportsCOVID-19 vaccineAdministrationPainHeadacheCOVID‐19 mRNA vaccine, but not a viral vector‐based vaccine, promotes neutralizing anti‐type I interferon autoantibody production in a small group of healthy individuals
Xu W, Wen X, Cong X, Jiang W. COVID‐19 mRNA vaccine, but not a viral vector‐based vaccine, promotes neutralizing anti‐type I interferon autoantibody production in a small group of healthy individuals. Journal Of Medical Virology 2023, 95: e29137. PMID: 37792386, PMCID: PMC10603818, DOI: 10.1002/jmv.29137.Peer-Reviewed Original ResearchConceptsViral vector-based vaccinesCOVID-19 mRNA vaccinesVector-based vaccinesGroup of healthy individualsMRNA vaccinesHealthy individualsPlasma levelsAnti-type I IFN autoantibodiesI interferonLevels of IgG autoantibodiesEvaluate plasma levelsHuman self-antigensPost-COVID-19 vaccinationCOVID-19 vaccineImpaired immune defenseInduce adverse eventsBaseline in vitroIncreased antibody levelsSARS-CoV-2 infectionSARS-CoV-2 antigensType I IFNType I interferonAutoantibody productionSelf-antigensInduce autoimmunityPrior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre N, Lutz R, Cruz I, Raddassi K, Ruff W, Racke M, Wilson J, Givens T, Grifoni A, Weiskopf D, Sette A, Kleinstein S, Montgomery R, Shaw A, Li F, Fan R, Hafler D, Tomayko M, Longbrake E. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023, 8: e168102. PMID: 37606046, PMCID: PMC10543713, DOI: 10.1172/jci.insight.168102.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinationB-cell-depleted patientsB-cell depletionAntibody responseMRNA vaccinationThird doseCell depletionT cellsClaude D. Pepper Older Americans Independence CenterB cellsNational Multiple Sclerosis SocietyAnti-CD20 antibodySpike-specific antibodiesMultiple Sclerosis SocietyLow cumulative exposureLogistic regression modelsImportant clinical needCD20 therapyCD20 treatmentMost patientsThird vaccineSerologic responseVaccine dosesMRNA vaccinesVaccination strategiesDevelopment 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 platformA mosquito AgTRIO mRNA vaccine contributes to immunity against malaria
Chuang Y, Alameh M, Abouneameh S, Raduwan H, Ledizet M, Weissman D, Fikrig E. A mosquito AgTRIO mRNA vaccine contributes to immunity against malaria. Npj Vaccines 2023, 8: 88. PMID: 37286568, PMCID: PMC10244833, DOI: 10.1038/s41541-023-00679-x.Peer-Reviewed Original ResearchHumoral responseFuture malaria vaccinesMosquito saliva proteinsRobust humoral responseImmunization of miceVector antigensIsotype antibodiesIgG titersImmunized miceMalaria vaccinePassive immunizationIgG2a isotypesMRNA vaccinesPlasmodium infectionMosquito bitesMRNA lipid nanoparticlesVaccineMRNA-LNPPlasmodium sporozoitesMalariaMiceImmunizationSaliva proteinsPotential usefulnessVertebrate hostsCytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis
Barmada A, Klein J, Ramaswamy A, Brodsky N, Jaycox J, Sheikha H, Jones K, Habet V, Campbell M, Sumida T, Kontorovich A, Bogunovic D, Oliveira C, Steele J, Hall E, Pena-Hernandez M, Monteiro V, Lucas C, Ring A, Omer S, Iwasaki A, Yildirim I, Lucas C. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Science Immunology 2023, 8: eadh3455-eadh3455. PMID: 37146127, PMCID: PMC10468758, DOI: 10.1126/sciimmunol.adh3455.Peer-Reviewed Original ResearchConceptsMRNA vaccinesSARS-CoV-2 mRNA vaccinesSARS-CoV-2 mRNA vaccinationC-reactive protein levelsB-type natriuretic peptidePeripheral blood mononuclear cellsCardiac tissue inflammationDeep immune profilingSerum soluble CD163Vaccine-associated myocarditisCohort of patientsBlood mononuclear cellsCytotoxic T cellsLate gadolinium enhancementHypersensitivity myocarditisElevated troponinMRNA vaccinationImaging abnormalitiesNK cellsImmune profilingKiller cellsMyeloid responseNatriuretic peptideHumoral mechanismsInflammatory cytokines
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