An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity

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 immu...

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Bibliographic Details
Published in:Cell 2022-02, Vol.185 (4), p.614-629.e21
Main Authors: 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
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Aluminum Hydroxide - chemistry
Animals
Antibodies, Neutralizing - immunology
Antibody Specificity - immunology
Antigens, Viral - immunology
B-Lymphocytes - immunology
beta-Glucans - metabolism
Candida albicans - chemistry
Chlorocebus aethiops
coronavirus
COVID-19 - immunology
COVID-19 - prevention & control
COVID-19 - virology
Dectin
Epitopes - immunology
Immunity, Innate
Immunization
inflammation
Inflammation - pathology
influenza A virus
innate immunity
interferon
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
PAMP
Paranasal Sinuses - metabolism
pathogen-associated molecular pattern
pattern recognition receptor
Protein Subunits - metabolism
PRR
SARS-CoV-2
Sialic Acid Binding Ig-like Lectin 1 - metabolism
Solubility
Spike Glycoprotein, Coronavirus - metabolism
T-Lymphocytes - immunology
Transcription Factor RelB - metabolism
Vero Cells
viral glycoprotein
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Summary: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. [Display omitted] •Size and solubility of microbial ligands determine the immune response•Fungal mannans are directly drained to the LN to drive cell accrual via interferon release•Tuning mannan physical properties broadens epitope specificity of SARS-CoV-2 anti-Spike antibodies•An adjuvant formulation of mannan/alum induces heterosubtypic immunity against IAV The physical properties of fungal mannans determine their immunological activity, and modulating their physical form improves the adjuvant properties of these immune stimuli when included in vaccine formulations directed against respiratory viruses.
ISSN:0092-8674
1097-4172
1097-4172
DOI:10.1016/j.cell.2022.01.009