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.
Abstract:
The development of vaccines against fungi and other intracellular microbes is impeded in part by a lack of suitable adjuvants. While most current vaccines against infectious diseases preferentially induce production of antibodies, cellular immunity is essential for the resolution of fungal infections. Microbes such as fungi and Mycobacterium tuberculosis require Th17 and Th1 cells for resistance, and engage the C-type lectin receptors including Dectin-2. Herein, we discovered a novel Dectin-2 ligand, the glycoprotein Blastomyces Eng2 (Bl-Eng2). Bl-Eng2 triggers robust signaling in Dectin-2 reporter cells and induces IL-6 in human PBMC and BMDC from wild type but not Dectin-2-/- and Card9-/- mice. The addition of Bl-Eng2 to a pan-fungal subunit vaccine primed large numbers of Ag-specific Th17 and Th1 cells, augmented activation and killing of fungi by myeloid effector cells, and protected mice from lethal fungal challenge, revealing Bl-Eng2's potency as a vaccine adjuvant. Thus, ligation of Dectin-2 by Bl-Eng-2 could be harnessed as a novel adjuvant strategy to protect against infectious diseases requiring cellular immunity.
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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