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
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 mo...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | article artículo publishedVersion |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2023
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/2133/25159 http://hdl.handle.net/2133/25159 |
| Aporte de: |
| id |
I15-R121-2133-25159 |
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| record_format |
dspace |
| institution |
Universidad Nacional de Rosario |
| institution_str |
I-15 |
| repository_str |
R-121 |
| collection |
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) |
| language |
Inglés |
| topic |
Mucosal adjuvant Protease inhibitor Structure-activity relationship Protein structure Protein crystallization |
| spellingShingle |
Mucosal adjuvant Protease inhibitor Structure-activity relationship Protein structure Protein crystallization Darriba, María Laura Pueblas Castro, Celeste Coria, Lorena M. Bruno, Laura Cerutti, María Laura Otero, Lisandro H. Chemes, Lucía B. Rasia, Rodolfo M. Klinke, Sebastián Cassataro, Juliana Pasquevich, Karina A. 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 |
| topic_facet |
Mucosal adjuvant Protease inhibitor Structure-activity relationship Protein structure Protein crystallization |
| description |
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. |
| format |
article artículo publishedVersion |
| author |
Darriba, María Laura Pueblas Castro, Celeste Coria, Lorena M. Bruno, Laura Cerutti, María Laura Otero, Lisandro H. Chemes, Lucía B. Rasia, Rodolfo M. Klinke, Sebastián Cassataro, Juliana Pasquevich, Karina A. |
| author_facet |
Darriba, María Laura Pueblas Castro, Celeste Coria, Lorena M. Bruno, Laura Cerutti, María Laura Otero, Lisandro H. Chemes, Lucía B. Rasia, Rodolfo M. Klinke, Sebastián Cassataro, Juliana Pasquevich, Karina A. |
| author_sort |
Darriba, María Laura |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Elsevier |
| publishDate |
2023 |
| url |
http://hdl.handle.net/2133/25159 http://hdl.handle.net/2133/25159 |
| work_keys_str_mv |
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Repositorios |
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1764820412802269185 |