Department of Medicine, Division of Infectious Diseases and Immunology
Bacterial Infections and Mycoses | Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Immunotherapy | Influenza Virus Vaccines
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.
Mannose, Vaccination and immunization, Immunologic adjuvants, Cloning, Respiratory infections, Cytotoxic T cells, Viral vaccines, Influenza A virus
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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.
DOI of Published Version
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
Dos Santos Dias L, Gomez CL, Specht CA, Levitz SM, Wuthrich M. (2021). Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. Open Access Publications by UMMS Authors. https://doi.org/10.1371/journal.ppat.1009324. Retrieved from https://escholarship.umassmed.edu/oapubs/4660
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Bacterial Infections and Mycoses Commons, Immunology of Infectious Disease Commons, Immunopathology Commons, Immunoprophylaxis and Therapy Commons, Immunotherapy Commons, Influenza Virus Vaccines Commons