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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Published inbioRxiv
Main Authors Lucas Dos Santos Dias, Dobson, Hannah E, Brock Kingstad Bakke, Kujoth, Greg C, Huang, Junfeng, Kohn, Elaine M, Cleison Ledesma Taira, Wang, Huafeng, Supekar, Nitin T, Azadi, Parastoo, Li, Lingjun, Marulasiddappa Suresh, Klein, Bruce Steven, Wuethrich, Marcel
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 25.06.2020
Subjects
Adjuvants
Antigens
CD4 antigen
CD8 antigen
Cell-mediated immunity
Endoglucanase
Fungi
Immunogenicity
Infectious diseases
Influenza
Influenza A
Mucosa
Polysaccharides
Vaccines
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Summary: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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.06.24.169763