Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009368/ https://www.ncbi.nlm.nih.gov/pubmed/33735218 http://dx.doi.org/10.1371/journal.ppat.1009324 |
_version_ | 1783672860060942336 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | dos Santos Dias, Lucas |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8009368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80093682021-04-07 Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity 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 PLoS Pathog Research Article 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. Public Library of Science 2021-03-18 /pmc/articles/PMC8009368/ /pubmed/33735218 http://dx.doi.org/10.1371/journal.ppat.1009324 Text en © 2021 dos Santos Dias et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article 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 Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009368/ https://www.ncbi.nlm.nih.gov/pubmed/33735218 http://dx.doi.org/10.1371/journal.ppat.1009324 |
work_keys_str_mv | AT dossantosdiaslucas structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT dobsonhannahe structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT bakkebrockkingstad structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT kujothgregoryc structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT huangjunfeng structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT kohnelainem structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT tairacleisonledesma structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT wanghuafeng structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT supekarnitint structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT fitesjscott structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT gatesdaisy structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT gomezchristinal structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT spechtcharlesa structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT levitzstuartm structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT azadiparastoo structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT lilingjun structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT sureshmarulasiddappa structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT kleinbruces structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity AT wuthrichmarcel structuralbasisofblastomycesendoglucanase2adjuvancyinantifungalandviralimmunity |