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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009324 |
| _version_ | 1819020354160427008 |
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| author | Lucas Dos Santos Dias Hannah E Dobson Brock Kingstad Bakke Gregory C Kujoth Junfeng Huang Elaine M Kohn Cleison Ledesma Taira Huafeng Wang Nitin T Supekar J Scott Fites Daisy Gates Christina L Gomez Charles A Specht Stuart M Levitz Parastoo Azadi Lingjun Li Marulasiddappa Suresh Bruce S Klein Marcel Wüthrich |
| author_facet | Lucas Dos Santos Dias Hannah E Dobson Brock Kingstad Bakke Gregory C Kujoth Junfeng Huang Elaine M Kohn Cleison Ledesma Taira Huafeng Wang Nitin T Supekar J Scott Fites Daisy Gates Christina L Gomez Charles A Specht Stuart M Levitz Parastoo Azadi Lingjun Li Marulasiddappa Suresh Bruce S Klein Marcel Wüthrich |
| author_sort | Lucas Dos Santos Dias |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T03:49:52Z |
| format | Article |
| id | doaj.art-fc7f3feb47ae4cc8a5f6edd4c6048362 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T03:49:52Z |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-fc7f3feb47ae4cc8a5f6edd4c60483622022-12-21T19:16:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-03-01173e100932410.1371/journal.ppat.1009324Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity.Lucas Dos Santos DiasHannah E DobsonBrock Kingstad BakkeGregory C KujothJunfeng HuangElaine M KohnCleison Ledesma TairaHuafeng WangNitin T SupekarJ Scott FitesDaisy GatesChristina L GomezCharles A SpechtStuart M LevitzParastoo AzadiLingjun LiMarulasiddappa SureshBruce S KleinMarcel WüthrichThe 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.https://doi.org/10.1371/journal.ppat.1009324 |
| spellingShingle | Lucas Dos Santos Dias Hannah E Dobson Brock Kingstad Bakke Gregory C Kujoth Junfeng Huang Elaine M Kohn Cleison Ledesma Taira Huafeng Wang Nitin T Supekar J Scott Fites Daisy Gates Christina L Gomez Charles A Specht Stuart M Levitz Parastoo Azadi Lingjun Li Marulasiddappa Suresh Bruce S Klein Marcel Wüthrich Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. PLoS Pathogens |
| title | Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. |
| title_full | Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. |
| title_fullStr | Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. |
| title_full_unstemmed | Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. |
| title_short | Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity. |
| title_sort | structural basis of blastomyces endoglucanase 2 adjuvancy in anti fungal and viral immunity |
| url | https://doi.org/10.1371/journal.ppat.1009324 |
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