RRC ID 80081
Author Borriello F, Poli V, Shrock E, Spreafico R, Liu X, Pishesha N, Carpenet C, Chou J, Di Gioia M, McGrath ME, Dillen CA, Barrett NA, Lacanfora L, Franco ME, Marongiu L, Iwakura Y, Pucci F, Kruppa MD, Ma Z, Lowman DW, Ensley HE, Nanishi E, Saito Y, O'Meara TR, Seo HS, Dhe-Paganon S, Dowling DJ, Frieman M, Elledge SJ, Levy O, Irvine DJ, Ploegh HL, Williams DL, Zanoni I.
Title An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity.
Journal Cell
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.
Volume 185(4)
Pages 614-629.e21
Published 2022-2-17
DOI 10.1016/j.cell.2022.01.009
PII S0092-8674(22)00067-8
PMID 35148840
PMC PMC8857056
MeSH Adjuvants, Immunologic / pharmacology* Aluminum Hydroxide / chemistry Animals Antibodies, Neutralizing / immunology Antibody Specificity / immunology Antigens, Viral / immunology* B-Lymphocytes / immunology COVID-19 / immunology COVID-19 / prevention & control COVID-19 / virology Candida albicans / chemistry* Chlorocebus aethiops Epitopes / immunology Immunity, Innate Immunization Inflammation / pathology Interferons / metabolism Lectins, C-Type / metabolism Ligands Lung / immunology Lung / pathology Lung / virology Lymph Nodes / immunology Lymph Nodes / metabolism Macrophages / metabolism Mannans / immunology* Mice Mice, Inbred C57BL Paranasal Sinuses / metabolism Protein Subunits / metabolism Sialic Acid Binding Ig-like Lectin 1 / metabolism Solubility Spike Glycoprotein, Coronavirus / metabolism T-Lymphocytes / immunology Transcription Factor RelB / metabolism Vero Cells beta-Glucans / metabolism
IF 38.637
Mice RBRC04395