Ligation of Dectin-2 with a novel microbial ligand promotes adjuvant activity for vaccination

Huafeng Wang1, Taek-Jin Lee1, Scott J Fites1

  • 1Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States of America.

Plos Pathogens
|August 10, 2017
PubMed

Insights

Researchers discovered a novel fungal glycoprotein, Blastomyces Eng2 (Bl-Eng2), that acts as a potent vaccine adjuvant. This Dectin-2 ligand enhances cellular immunity, protecting against lethal fungal infections by boosting Th17 and Th1 cell responses.

Area of Science:

  • Immunology
  • Microbiology
  • Vaccinology

Background:

  • Cellular immunity, particularly Th17 and Th1 cells, is crucial for combating fungal infections, unlike antibody-focused vaccines.
  • Intracellular microbes like fungi and Mycobacterium tuberculosis rely on C-type lectin receptors, including Dectin-2, for immune engagement.
  • Developing effective adjuvants that promote cellular immunity is a key challenge in vaccine development.

Purpose of the Study:

  • To identify and characterize novel ligands for Dectin-2 that can serve as vaccine adjuvants.
  • To evaluate the potential of a newly discovered glycoprotein, Blastomyces Eng2 (Bl-Eng2), as an adjuvant for vaccines targeting fungal infections.

Main Methods:

  • Investigated Bl-Eng2's interaction with Dectin-2 using reporter cell assays.
  • Assessed Bl-Eng2's ability to induce cytokine production (IL-6) in human peripheral blood mononuclear cells (PBMCs) and bone marrow-derived dendritic cells (BMDCs).
  • Evaluated the adjuvant efficacy of Bl-Eng2 in a pan-fungal subunit vaccine model in mice, assessing immune cell responses and protection against fungal challenge.

Main Results:

  • Bl-Eng2 was identified as a novel Dectin-2 ligand, triggering significant signaling in Dectin-2 reporter cells.
  • Bl-Eng2 induced IL-6 production in human PBMCs and BMDCs from wild-type mice, but not from Dectin-2 or Card9 knockout mice, confirming Dectin-2-dependent signaling.
  • In vivo, Bl-Eng2 as an adjuvant amplified antigen-specific Th17 and Th1 cell populations, enhanced myeloid cell activation and fungal killing, and conferred protection against lethal fungal challenge.

Conclusions:

  • Bl-Eng2 is a potent Dectin-2 ligand with significant adjuvant properties for vaccines requiring cellular immunity.
  • Ligation of Dectin-2 by Bl-Eng2 represents a promising novel adjuvant strategy for enhancing protection against fungal and potentially other intracellular microbial infections.
  • This discovery opens new avenues for developing vaccines that effectively elicit cellular immune responses critical for pathogen clearance.

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