Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity
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...
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| Veröffentlicht in: | PLoS pathogens 2021-03, Vol.17 (3), p.e1009324-e1009324 |
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| creator | Dos Santos Dias, Lucas Dobson, Hannah E Bakke, Brock Kingstad Kujoth, Gregory C Huang, Junfeng Kohn, Elaine M Taira, Cleison Ledesma Wang, Huafeng Supekar, Nitin T Fites, J Scott Gates, Daisy Gomez, Christina L Specht, Charles A Levitz, Stuart M Azadi, Parastoo Li, Lingjun Suresh, Marulasiddappa Klein, Bruce S Wüthrich, Marcel |
| description | 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. |
| doi_str_mv | 10.1371/journal.ppat.1009324 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1009324</identifier><identifier>PMID: 33735218</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antibodies ; Antigen-antibody reactions ; Antigens ; Backbone ; Biology and Life Sciences ; Cell walls ; Cytokines ; E coli ; Endoglucanase ; Endopeptidase K ; Enzymes ; Fungi ; Fungicides ; Genetic aspects ; Glycan ; Glycoproteins ; Health aspects ; Hemagglutinins ; Host-parasite relationships ; Infections ; Influenza ; Ligands ; Lymphocytes ; Medicine and Health Sciences ; Mycoses ; Observations ; Pathogens ; Phosphorylation ; Physical Sciences ; Polysaccharides ; Protein structure ; Proteinase ; Proteins ; Recognition ; Research and Analysis Methods ; Risk factors ; Vaccines ; Viral infections ; Yeasts</subject><ispartof>PLoS pathogens, 2021-03, Vol.17 (3), p.e1009324-e1009324</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 dos Santos Dias et al. 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| identifier | ISSN: 1553-7374 |
| ispartof | PLoS pathogens, 2021-03, Vol.17 (3), p.e1009324-e1009324 |
| issn | 1553-7374 1553-7366 1553-7374 |
| language | eng |
| recordid | cdi_plos_journals_2513689710 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Antibodies Antigen-antibody reactions Antigens Backbone Biology and Life Sciences Cell walls Cytokines E coli Endoglucanase Endopeptidase K Enzymes Fungi Fungicides Genetic aspects Glycan Glycoproteins Health aspects Hemagglutinins Host-parasite relationships Infections Influenza Ligands Lymphocytes Medicine and Health Sciences Mycoses Observations Pathogens Phosphorylation Physical Sciences Polysaccharides Protein structure Proteinase Proteins Recognition Research and Analysis Methods Risk factors Vaccines Viral infections Yeasts |
| title | Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T00%3A35%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structural%20basis%20of%20Blastomyces%20Endoglucanase-2%20adjuvancy%20in%20anti-fungal%20and%20-viral%20immunity&rft.jtitle=PLoS%20pathogens&rft.au=Dos%20Santos%20Dias,%20Lucas&rft.date=2021-03-01&rft.volume=17&rft.issue=3&rft.spage=e1009324&rft.epage=e1009324&rft.pages=e1009324-e1009324&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1009324&rft_dat=%3Cgale_plos_%3EA658713273%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2513689710&rft_id=info:pmid/33735218&rft_galeid=A658713273&rft_doaj_id=oai_doaj_org_article_fc7f3feb47ae4cc8a5f6edd4c6048362&rfr_iscdi=true |