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

Author

Francesco Borriello, Valentina Poli, Ellen Shrock, Roberto Spreafico, Xin Liu, Novalia Pishesha, Claire Carpenet, Janet Chou, Marco Di Gioia, Marisa E. McGrath, Carly A. Dillen, Nora A. Barrett, Lucrezia Lacanfora, Marcella E. Franco, Laura Marongiu, Yoichiro Iwakura, Ferdinando Pucci, Michael D. Kruppa, Zuchao Ma, Douglas W. Lowman, Harry E. Ensley, Etsuro Nanishi, Yoshine Saito, Timothy R. O’Meara, Hyuk-Soo Seo, Sirano Dhe-Paganon, David J. Dowling, Matthew Frieman, Stephen J. Elledge, Ofer Levy, Darrell J. Irvine, Hidde L. Ploegh, David L. Williams, Ivan Zanoni, Borriello, F, Poli, V, Shrock, E, Spreafico, R, Liu, X, Pishesha, N, Carpenet, C, Chou, J, Di Gioia, M, Mcgrath, M, Dillen, C, Barrett, N, Lacanfora, L, Franco, M, Marongiu, L, Iwakura, Y, Pucci, F, Kruppa, M, Ma, Z, Lowman, D, Ensley, H, Nanishi, E, Saito, Y, O'Meara, T, Seo, H, Dhe-Paganon, S, Dowling, D, Frieman, M, Elledge, S, Levy, O, Irvine, D, Ploegh, H, Williams, D, and Zanoni, I

Subjects
beta-Glucans, PRR, pattern recognition receptor, Sialic Acid Binding Ig-like Lectin 1, T-Lymphocytes, influenza A viru, Aluminum Hydroxide, viral glycoprotein, Ligands, General Biochemistry, Genetics and Molecular Biology, Mannans, Epitopes, Adjuvants, Immunologic, Antibody Specificity, Candida albicans, Chlorocebus aethiops, Paranasal Sinuses, Animals, Lectins, C-Type, innate immunity, Antigens, Viral, Lung, Vero Cells, Dectin, Inflammation, B-Lymphocytes, SARS-CoV-2, Macrophages, Transcription Factor RelB, COVID-19, interferon, PAMP, pathogen-associated molecular pattern, Antibodies, Neutralizing, Immunity, Innate, coronaviru, Mice, Inbred C57BL, Protein Subunits, Solubility, Spike Glycoprotein, Coronavirus, Immunization, Interferons, Lymph Nodes
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.

Published
2022

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