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

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. LowmanHarry 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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)614-629.e21
JournalCell
Volume185
Issue number4
DOIs
Publication statusPublished - 17 Feb 2022

Keywords

  • Dectin
  • PAMP
  • PRR
  • SARS-CoV-2
  • coronavirus
  • inflammation
  • influenza A virus
  • innate immunity
  • interferon
  • pathogen-associated molecular pattern
  • pattern recognition receptor
  • viral glycoprotein

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