2023
Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination
Suberi A, Grun M, Mao T, Israelow B, Reschke M, Grundler J, Akhtar L, Lee T, Shin K, Piotrowski-Daspit A, Homer R, Iwasaki A, Suh H, Saltzman W. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination. Science Translational Medicine 2023, 15: eabq0603. PMID: 37585505, PMCID: PMC11137749, DOI: 10.1126/scitranslmed.abq0603.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Lethal viral challengeAntigen-presenting cellsSyndrome coronavirus 2Humoral adaptive immunityLung-targeting deliveryIntranasal vaccinationMucosal vaccinationPulmonary diseaseMucosal vaccinesSusceptible miceCoronavirus 2Viral challengeAdaptive immunityLungTranslational potentialMessenger RNA (mRNA) therapeuticsVaccinationMRNADeliveryTherapeuticsRNA therapeuticsTherapeutic deliverySARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity
Jaycox J, Lucas C, Yildirim I, Dai Y, Wang E, Monteiro V, Lord S, Carlin J, Kita M, Buckner J, Ma S, Campbell M, Ko A, Omer S, Lucas C, Speake C, Iwasaki A, Ring A. SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity. Nature Communications 2023, 14: 1299. PMID: 36894554, PMCID: PMC9996559, DOI: 10.1038/s41467-023-36686-8.Peer-Reviewed Original ResearchConceptsVaccine-associated myocarditisAutoimmune patientsAutoantibody reactivitySARS-CoV-2 mRNA vaccinationVaccine-related adverse effectsSARS-CoV-2 immunitySARS-CoV-2 infectionAcute COVID-19Development of autoantibodiesCOVID-19 patientsAnti-viral immunityVirus-specific antibodiesCOVID-19 vaccineCOVID-19Humoral autoimmunityMRNA vaccinationAutoantibody responsePost vaccinationAutoantibody developmentAutoimmune diseasesHumoral responseHealthy individualsPatientsAntigen profilingAdverse effects
2022
Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis
Lind M, Robertson A, Silva J, Warner F, Coppi A, Price N, Duckwall C, Sosensky P, Di Giuseppe E, Borg R, Fofana M, Ranzani O, Dean N, Andrews J, Croda J, Iwasaki A, Cummings D, Ko A, Hitchings M, Schulz W. Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis. PLOS Medicine 2022, 19: e1004136. PMID: 36454733, PMCID: PMC9714718, DOI: 10.1371/journal.pmed.1004136.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionBooster vaccinationPrior infectionOmicron infectionPrimary vaccinationMRNA vaccinationOdds ratioAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionPrior SARS-CoV-2 infectionTest-negative case-control analysisYale New Haven Health SystemTest-negative case-control studyCOVID-19 mRNA vaccinationSyndrome coronavirus 2 infectionOmicron variant infectionPrior infection statusCoronavirus 2 infectionCase-control studyCase-control analysisOdds of infectionRisk of infectionRace/ethnicityBooster dosesDate of testUnadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses
Mao T, Israelow B, Peña-Hernández MA, Suberi A, Zhou L, Luyten S, Reschke M, Dong H, Homer RJ, Saltzman WM, Iwasaki A. Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses. Science 2022, 378: eabo2523. PMID: 36302057, PMCID: PMC9798903, DOI: 10.1126/science.abo2523.Peer-Reviewed Original ResearchConceptsRespiratory mucosaSystemic immunityLethal SARS-CoV-2 infectionAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicSARS-CoV-2 infectionProtective mucosal immunityCross-reactive immunityT cell responsesCoronavirus 2 pandemicPrimary vaccinationParenteral vaccinesMucosal immunityVaccine strategiesRespiratory tractImmunoglobulin AMemory BImmune memoryPartial immunityCell responsesPoor immunityImmunitySpike proteinMucosaVaccineNo evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
Lu-Culligan A, Tabachnikova A, Pérez-Then E, Tokuyama M, Lee HJ, Lucas C, Monteiro V, Miric M, Brache V, Cochon L, Muenker MC, Mohanty S, Huang J, Kang I, Dela Cruz C, Farhadian S, Campbell M, Yildirim I, Shaw AC, Ma S, Vermund SH, Ko AI, Omer SB, Iwasaki A. No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination. PLOS Biology 2022, 20: e3001506. PMID: 35609110, PMCID: PMC9129011, DOI: 10.1371/journal.pbio.3001506.Peer-Reviewed Original ResearchConceptsCOVID-19 mRNA vaccinationMRNA vaccinationEarly pregnancyFetal sizeCoronavirus disease 2019 (COVID-19) mRNA vaccinationSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Maternal antibody statusAdverse neonatal outcomesSyndrome coronavirus 2Birth defectsPolyinosinic-polycytidylic acidCrown-rump lengthGross birth defectsUnvaccinated adultsMaternal illnessNeonatal outcomesVaccinated adultsAntibody statusTLR3 agonistEarly immunizationMurine pregnancyAntibody inductionCoronavirus 2Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination
Pérez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, Vogels CBF, Malik AA, De la Cruz E, Jorge A, De los Santos M, Leon P, Breban MI, Billig K, Yildirim I, Pearson C, Downing R, Gagnon E, Muyombwe A, Razeq J, Campbell M, Ko AI, Omer SB, Grubaugh ND, Vermund SH, Iwasaki A. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nature Medicine 2022, 28: 481-485. PMID: 35051990, PMCID: PMC8938264, DOI: 10.1038/s41591-022-01705-6.Peer-Reviewed Original ResearchConceptsTwo-dose regimenOmicron variantVaccine boosterMRNA vaccinesNeutralization activityDelta variantTwo-dose mRNA vaccinesVirus-specific antibody levelsSARS-CoV-2 Omicron variantMRNA vaccine boosterNeutralization of OmicronNumerous spike mutationsSARS-CoV-2 DeltaPotent neutralization activityInfection-induced immunityCOVID-19 vaccineBNT162b2 boosterBooster vaccinationPrime vaccinationAntibody levelsAntibody titersHumoral immunityImmune escapeInactivated vaccinesVaccine
2021
COVID-19 vaccines: Keeping pace with SARS-CoV-2 variants
Cevik M, Grubaugh ND, Iwasaki A, Openshaw P. COVID-19 vaccines: Keeping pace with SARS-CoV-2 variants. Cell 2021, 184: 5077-5081. PMID: 34534444, PMCID: PMC8445744, DOI: 10.1016/j.cell.2021.09.010.Peer-Reviewed Original Research
2020
Why and How Vaccines Work
Iwasaki A, Omer SB. Why and How Vaccines Work. Cell 2020, 183: 290-295. PMID: 33064982, PMCID: PMC7560117, DOI: 10.1016/j.cell.2020.09.040.Peer-Reviewed Original Research
2012
A vaccine strategy that protects against genital herpes by establishing local memory T cells
Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012, 491: 463-467. PMID: 23075848, PMCID: PMC3499630, DOI: 10.1038/nature11522.Peer-Reviewed Original Research
2008
Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node
Thompson JM, Nicholson MG, Whitmore AC, Zamora M, West A, Iwasaki A, Staats HF, Johnston RE. Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node. The Journal Of Immunology 2008, 181: 574-585. PMID: 18566424, PMCID: PMC3603373, DOI: 10.4049/jimmunol.181.1.574.Peer-Reviewed Original ResearchConceptsDraining Lymph NodesVirus replicon particlesMucosal immune responsesMucosal lymphoid tissuesImmune inductionAg deliveryIgA AbsLymph nodesLymphoid tissueImmune responseMucosal surfacesMucosal addressin cell adhesion molecule-1Strong mucosal immune responsesEncephalitis virus replicon particlesCell adhesion molecule-1Multiple mucosal surfacesViral-based vaccinesAdhesion molecule-1Lymphoid structuresIL-6Immunological parametersImmunological componentsCC chemokinesIgA detectionReplicon particles