UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2021-03-18

Document Type

Article

Disciplines

Bacterial Infections and Mycoses | Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Immunotherapy | Influenza Virus Vaccines

Abstract

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.

Keywords

Mannose, Vaccination and immunization, Immunologic adjuvants, Cloning, Respiratory infections, Cytotoxic T cells, Viral vaccines, Influenza A virus

Rights and Permissions

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.

DOI of Published Version

10.1371/journal.ppat.1009324

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

Journal/Book/Conference Title

PLoS pathogens

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33735218

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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