An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity
Name
nihms-1772871.pdf
Description
Accepted version
Size
2.15 MB
Format
Adobe PDF
Checksum (MD5)
ca484fc9d3b9249aceff541947a22c13
Author(s)
Irvine, Darrell
Date Issued
2022
Journal
Cell
Publisher
Elsevier BV
Citation
Irvine, Darrell. 2022. "An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity." Cell, 185 (4).
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Howard Hughes Medical Institute
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2022.01.009
