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An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity.
Borriello, Francesco; Poli, Valentina; Shrock, Ellen; Spreafico, Roberto; Liu, Xin; Pishesha, Novalia; Carpenet, Claire; Chou, Janet; Di Gioia, Marco; McGrath, Marisa E; Dillen, Carly A; Barrett, Nora A; Lacanfora, Lucrezia; Franco, Marcella E; Marongiu, Laura; Iwakura, Yoichiro; Pucci, Ferdinando; Kruppa, Michael D; Ma, Zuchao; Lowman, Douglas W; Ensley, Harry E; Nanishi, Etsuro; Saito, Yoshine; O'Meara, Timothy R; Seo, Hyuk-Soo; Dhe-Paganon, Sirano; Dowling, David J; Frieman, Matthew; Elledge, Stephen J; Levy, Ofer; Irvine, Darrell J; Ploegh, Hidde L; Williams, David L; Zanoni, Ivan.
  • Borriello F; Harvard 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.
  • Poli V; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
  • Shrock E; Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Boston, MA, USA.
  • Spreafico R; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
  • Liu X; Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Pishesha N; Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Carpenet C; Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Chou J; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
  • Di Gioia M; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Division of Immunology, Boston, MA, USA.
  • McGrath ME; University of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, MD, USA.
  • Dillen CA; University of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, MD, USA.
  • Barrett NA; Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Division of Allergy and Clinical Immunology, Boston, MA, USA.
  • Lacanfora L; Harvard 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.
  • Franco ME; Harvard 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.
  • Marongiu L; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • Iwakura Y; Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Tokyo, Japan.
  • Pucci F; Department of Otolaryngology-Head and Neck Surgery, Department of Cell, Developmental & Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Kruppa MD; Department of Biomedical Sciences, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
  • Ma Z; Department of Surgery, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
  • Lowman DW; Department of Surgery, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
  • Ensley HE; Department of Surgery, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
  • Nanishi E; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
  • Saito Y; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
  • O'Meara TR; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
  • Seo HS; Harvard Medical School, Boston, MA, USA; Dana-Farber Cancer Institute, Department of Cancer Biology, Boston, MA, USA.
  • Dhe-Paganon S; Harvard Medical School, Boston, MA, USA; Dana-Farber Cancer Institute, Department of Cancer Biology, Boston, MA, USA.
  • Dowling DJ; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA.
  • Frieman M; University of Maryland School of Medicine, Department of Microbiology and Immunology, Baltimore, MD, USA.
  • Elledge SJ; Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Program in Virology, Boston, MA, USA.
  • Levy O; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Precision Vaccines Program, Boston, MA, USA; Broad Institute of MIT & Harvard, Cambridge, MA, USA.
  • Irvine DJ; Massachusetts 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.
  • Ploegh HL; Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Williams DL; Department of Biomedical Sciences, Quillen College of Medicine, Center of Excellence in Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN, USA.
  • Zanoni I; Harvard 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.
Cell ; 185(4): 614-629.e21, 2022 02 17.
Article in English | MEDLINE | ID: covidwho-1676664
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Candida albicans / Adjuvants, Immunologic / Mannans / Antigens, Viral Type of study: Diagnostic study / Prognostic study Topics: Vaccines Language: English Journal: Cell Year: 2022 Document Type: Article Affiliation country: J.cell.2022.01.009

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Candida albicans / Adjuvants, Immunologic / Mannans / Antigens, Viral Type of study: Diagnostic study / Prognostic study Topics: Vaccines Language: English Journal: Cell Year: 2022 Document Type: Article Affiliation country: J.cell.2022.01.009