ArticleCell2022
An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity.
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Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57citing papers in PubMed
9.6field-weighted citation impact, top 1% of its field
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Who cites it
57 citing papers in PubMed, 116 citations in OpenAlex.
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- Identification of Mannose-Capped-Arabinomannan 101-mer as a Potential Influenza Virus Vaccine Adjuvant.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Nano-adjuvants enhance the immunogenicity and safety of infectious bursal disease virus vaccines: a comprehensive review.Frontiers in immunology · 2026Review
- Discovery of a small molecule TLR3 agonist adjuvant.Nature communications · 2025Article
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- Neutrophil extracellular traps (NETs)-score: a novel prognostic marker for colorectal cancer patients.Discover oncology · 2025Article
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- Construction and evaluation of recombinant Lactobacillus plantarum expressing Micropterus salmoides hepcidin.Microbial cell factories · 2025Article
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- Microbiota mechanisms in cancer progression and therapy.Cell chemical biology · 2025Review
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Authors and funding
34 authors at 11 institutions in 3 countries.
Francesco BorrielloHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA; Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Valentina PoliHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Ellen ShrockHarvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Boston, MA, USA.
Roberto SpreaficoInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
Xin LiuHarvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Novalia PisheshaHarvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Claire CarpenetHarvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Janet ChouHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Marco Di GioiaHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
Marisa E McGrathUniversity of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, MD, USA.
Carly A DillenUniversity of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, MD, USA.
Nora A BarrettHarvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Division of Allergy and Clinical Immunology, Boston, MA, USA.
Lucrezia LacanforaHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Marcella E FrancoHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Laura MarongiuDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Yoichiro IwakuraCenter for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Tokyo, Japan.
Ferdinando PucciDepartment of Otolaryngology-Head and Neck Surgery, Department of Cell, Developmental & Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Michael D KruppaDepartment of Biomedical Sciences, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
Zuchao MaDepartment of Surgery, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
Douglas W LowmanDepartment of Surgery, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
Harry E EnsleyDepartment of Surgery, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
Etsuro NanishiHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
Yoshine SaitoBoston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
Timothy R O'MearaBoston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
Hyuk-Soo SeoHarvard Medical School, Boston, MA, USA; Dana-Farber Cancer Institute, Department of Cancer Biology, Boston, MA, USA.
Sirano Dhe-PaganonHarvard Medical School, Boston, MA, USA; Dana-Farber Cancer Institute, Department of Cancer Biology, Boston, MA, USA.
David J DowlingHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
Matthew FriemanUniversity of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, MD, USA.
Stephen J ElledgeHarvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Boston, MA, USA.
Ofer LevyHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA; Broad Institute of MIT & Harvard, Cambridge, MA, USA.
Darrell J IrvineMassachusetts Institute of Technology, Department of Biological Engineering and Department of Materials Science and Engineering, Koch Institute for Integrative Cancer Research, Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Hidde L PloeghHarvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
David L WilliamsDepartment of Biomedical Sciences, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
Ivan ZanoniHarvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA; Boston Children's Hospital, Division of Gastroenterology, Boston, MA, USA. Electronic address: ivan.zanoni@childrens.harvard.edu.
Boston Children's Hospital · USEast Tennessee State University · USBrigham and Women's Hospital · USUniversity of Maryland, Baltimore · USHarvard University · USBroad Institute · USHoward Hughes Medical Institute · USOregon Health & Science University · USQB3 · USTokyo University of Science · JPUniversity of Milano-Bicocca · IT
Funding
Small-molecule adjuvants to enhance the efficacy of flu vaccines in newborns and the elderly75N93019C00044 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2019 to 2023
$11.0MQuillen College of Medicine Building 119 RenovationC06RR030651 · NCRR · EAST TENNESSEE STATE UNIVERSITY · PI ORDWAY, GREGORY ALLEN · 2010 to 2010
$9.1MType III interferon Control of Mucosal ImmunityR01DK115217 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Scott B Snapper, Ivan Zanoni · 2017 to 2026
$5.6MInnate control of the inflammatory process during fungal infectionsR01AI121066 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI ZANONI, IVAN · 2016 to 2025
$4.8MDevelopment of a novel adjuvant strategy enabled by modulation of the physical properties of fungal mannansR01AI165505 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Ivan Zanoni · 2021 to 2026
$4.6MTraining Innate Immunity: A new approach to the treatment of SepsisR01GM119197 · NIGMS · EAST TENNESSEE STATE UNIVERSITY · PI SHERWOOD, EDWARD R, WILLIAMS, DAVID L. · 2016 to 2024
$4.6MInnate Immunity and Cardiovascular Function in SepsisR01GM083016 · NIGMS · EAST TENNESSEE STATE UNIVERSITY · PI LI, CHUANFU, WILLIAMS, DAVID L. · 2009 to 2021
$3.8MRole of Diabetes in MERS Coronavirus PathogenesisR01AI148166 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI FRIEMAN, MATTHEW BRYAN · 2020 to 2023
$2.3MLeveraging immunostimulatory pathways that enhance BCG vaccination for the rational design of synthetic neonatal vaccine formulationsR21AI137932 · NIAID · NORTHWESTERN UNIVERSITY · PI DOWLING, DAVID JAMES, SCOTT, EVAN ALEXANDER · 2019 to 2020
$468kBroad Spectrum Anti-viral Compounds Targeting the SKI ComplexR21AI153480 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI FRIEMAN, MATTHEW BRYAN · 2020 to 2021
$425kGenetic Characterization of phosphomannan biosynthesis in C. aurisR21AI159877 · NIAID · EAST TENNESSEE STATE UNIVERSITY · PI KRUPPA, MICHAEL D · 2021 to 2022
$407kNCRR NIH HHS C06 RR030651NIAID NIH HHS 75N93019C00044NIAID NIH HHS 75N93020C00038NIAID NIH HHS R01 AI121066NIAID NIH HHS R01 AI148166NIAID NIH HHS R01 AI165505NIAID NIH HHS R21 AI137932NIAID NIH HHS R21 AI153480NIAID NIH HHS R21 AI159877NIDDK NIH HHS R01 DK115217NIGMS NIH HHS R01 GM083016NIGMS NIH HHS R01 GM119197
Abstract
Activation of the innate immune system via pattern recognition receptors (PRRs) is key to generate lasting adaptive immunity. PRRs detect unique chemical patterns associated with invading microorganisms, but whether and how the physical properties of PRR ligands influence the development of the immune response remains unknown. Through the study of fungal mannans, we show that the physical form of PRR ligands dictates the immune response. Soluble mannans are immunosilent in the periphery but elicit a potent pro-inflammatory response in the draining lymph node (dLN). By modulating the physical form of mannans, we developed a formulation that targets both the periphery and the dLN. When combined with viral glycoprotein antigens, this mannan formulation broadens epitope recognition, elicits potent antigen-specific neutralizing antibodies, and confers protection against viral infections of the lung. Thus, the physical properties of microbial ligands determine the outcome of the immune response and can be harnessed for vaccine development.
Indexed as
Adjuvants, ImmunologicAluminum HydroxideAnimalsAntibodies, NeutralizingAntibody SpecificityAntigens, Viralbeta-GlucansB-LymphocytesCandida albicansChlorocebus aethiopsCOVID-19EpitopesImmunity, InnateImmunizationInflammationInterferonsAdjuvants, ImmunologicAluminum HydroxideAntibodies, NeutralizingAntigens, Viralbeta-Glucansdectin-2, mouseEpitopesInterferonsLectins, C-TypeLigandsMannansProtein SubunitsRelb protein, mouseSialic Acid Binding Ig-like Lectin 1Spike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Transcription Factor RelBcoronavirusDectininflammationinfluenza A virusinnate immunityinterferonPAMPpathogen-associated molecular patternpattern recognition receptorPRRSARS-CoV-2viral glycoprotein
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