A disordered region retains the full protease inhibitor activity and the capacity to induce CD8+ T cells in vivo of the oral vaccine adjuvant U-Omp19

A disordered region retains the full protease inhibitor activity and the capacity to induce CD8+ T cells in vivo of the oral vaccine adjuvant U-Omp19

[Display omitted] U-Omp19 is a bacterial protease inhibitor from Brucella abortus that inhibits gastrointestinal and lysosomal proteases, enhancing the half-life and immunogenicity of co-delivered antigens. U-Omp19 is a novel adjuvant that is in preclinical development with various vaccine candidate...

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Published in:Computational and structural biotechnology journal Vol. 20; pp. 5098 - 5114
Main Authors: Laura Darriba, M., Castro, Celeste Pueblas, Coria, Lorena M., Bruno, Laura, Laura Cerutti, M., Otero, Lisandro H., Chemes, Lucía B., Rasia, Rodolfo M., Klinke, Sebastián, Cassataro, Juliana, Pasquevich, Karina A.
Format: Journal Article
Language:English
Published: Elsevier B.V 2022
Elsevier
Subjects:
Mucosal adjuvant
Protease inhibitor
Protein crystallization
Protein structure
Structure-activity relationship
CD
Protein crystallization
IMAC
TEV
U-Omp19
MW
GdmCl
Mucosal adjuvant
SEC
NMR
IDP
Structure-activity relationship
MBP
SLS
Protein structure
Protease inhibitor
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Summary:[Display omitted] U-Omp19 is a bacterial protease inhibitor from Brucella abortus that inhibits gastrointestinal and lysosomal proteases, enhancing the half-life and immunogenicity of co-delivered antigens. U-Omp19 is a novel adjuvant that is in preclinical development with various vaccine candidates. However, the molecular mechanisms by which it exerts these functions and the structural elements responsible for these activities remain unknown. In this work, a structural, biochemical, and functional characterization of U-Omp19 is presented. Dynamic features of U-Omp19 in solution by NMR and the crystal structure of its C-terminal domain are described. The protein consists of a compact C-terminal beta-barrel domain and a flexible N-terminal domain. The latter domain behaves as an intrinsically disordered protein and retains the full protease inhibitor activity against pancreatic elastase, papain and pepsin. This domain also retains the capacity to induce CD8+ T cells in vivo of U-Omp19. This information may lead to future rationale vaccine designs using U-Omp19 as an adjuvant to deliver other proteins or peptides in oral formulations against infectious diseases, as well as to design strategies to incorporate modifications in its structure that may improve its adjuvanticity.
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ISSN:2001-0370
2001-0370
DOI:10.1016/j.csbj.2022.08.054