Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity
Authors
Dos Santos Dias, LucasGomez, Christina L.
Specht, Charles A.
Levitz, Stuart M.
Wuthrich, Marcel
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2021-03-18Keywords
MannoseVaccination and immunization
Immunologic adjuvants
Cloning
Respiratory infections
Cytotoxic T cells
Viral vaccines
Influenza A virus
Bacterial Infections and Mycoses
Immunology of Infectious Disease
Immunopathology
Immunoprophylaxis and Therapy
Immunotherapy
Influenza Virus Vaccines
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Show full item recordAbstract
The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.Source
Dos Santos Dias L, Dobson HE, Bakke BK, Kujoth GC, Huang J, Kohn EM, Taira CL, Wang H, Supekar NT, Fites JS, Gates D, Gomez CL, Specht CA, Levitz SM, Azadi P, Li L, Suresh M, Klein BS, Wüthrich M. Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. PLoS Pathog. 2021 Mar 18;17(3):e1009324. doi: 10.1371/journal.ppat.1009324. PMID: 33735218; PMCID: PMC8009368. Link to article on publisher's site
DOI
10.1371/journal.ppat.1009324Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41856PubMed ID
33735218Notes
Full author list omitted for brevity. For the full list of authors, see article.
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Copyright: © 2021 dos Santos Dias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1009324
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Except where otherwise noted, this item's license is described as Copyright: © 2021 dos Santos Dias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.