Estudios estructurales y funcionales de proteínas superficiales (capa S) de lactobacilos para su aplicación al desarrollo de nuevos adyuvantes vacunales
Cargando...
Fecha
2023-11-21
Título de la revista
ISSN de la revista
Título del volumen
Editor
Resumen
La capa S es una envoltura (glico)-proteica bidimensional auto-ensamblada presente en numerosas bacterias a la que se han atribuido diversas funciones. Las subunidades aisladas de proteína (SLP) se auto-ensamblan formando arreglos regulares a escala nanométrica, y en estudios in vitro realizados previamente, demostramos que la SLP de Lactobacillus kefiri CIDCA 8348 (SLP- 8348) potencia la respuesta de macrófagos murinos al LPS de manera Ca+2-dependiente, sugiriendo la participación de los glicanos y su reconocimiento por receptores de lectina tipo-C (CLR). Por ello, decidimos estudiar la inmunogenicidad de las SLP de L. kefiri y su capacidad potenciar la inmunidad adaptativa específica frente a otros antígenos (efecto adyuvante), a la vez que buscamos conocer aspectos de la estructura que pudieran influir en su auto-ensamblado en solución.
Durante el desarrollo del proyecto demostramos que las SLP provenientes de tres cepas de
L. kefiri son capaces de activar células presentadoras de antígeno y potenciar la activación inducida por LPS a través del reconocimiento vía CLR, lo que redunda en una mayor capacidad para estimular LTCD4+ antígeno-específicos. Las SLP-8321 y SLP-8348 ejercen su efecto vía Mincle, mientras que la SLP-5818 lo hace a través de SignR3. Asimismo, estudios in vivo permitieron demostrar la importancia de la integridad de los glicanos en la inmunogenicidad y en la adyuvanticidad de la SLP- 8348. Mediante TEM demostramos que la SLP-8348 adopta una geometría hexagonal al auto- ensamblarse en solución.
Por lo tanto, las SLP de L. kefiri emergen como herramientas valiosas para el desarrollo nuevos adyuvantes vacunales provenientes de bacterias seguras.
- The S-layer is a two-dimensional self-assembled (glyco)-protein envelope present in numerous bacteria to which various functions have been attributed. Isolated protein subunits (SLP) self-assemble into regular nanometer-scale arrays, and in previously performed in vitro studies, we demonstrated that SLP from Lactobacillus kefiri CIDCA 8348 (SLP-8348) potentiates the murine macrophage response to LPS in a Ca+2-dependent manner, suggesting the involvement of glycans and their recognition by C-type lectin receptors (CLRs). Therefore, we decided to study the immunogenicity of L. kefiri SLPs and their ability to enhance specific adaptive immunity against other antigens (adjuvant effect), while seeking to understand aspects of the structure that could influence their self-assembly in solution. During the development of the project, we were able to prove that SLPs from three strains of L. kefiri activate antigen-presenting cells and enhance LPS-induced activation through recognition via CLR, resulting in a greater capacity to stimulate antigen-specific LTCD4+. SLP-8321 and SLP- 8348 exert their effect via Mincle, while SLP-5818 does so through SignR3. In vivo studies have also demonstrated the importance of glycan integrity in the immunogenicity and adjuvant capacity of SLP- 8348. By TEM we demonstrated that SLP-8348 adopts a hexagonal geometry upon self-assembly in solution. Therefore, SLPs from L. kefiri emerge as valuable tools for the development of novel vaccine adjuvants from safe bacteria.
- The S-layer is a two-dimensional self-assembled (glyco)-protein envelope present in numerous bacteria to which various functions have been attributed. Isolated protein subunits (SLP) self-assemble into regular nanometer-scale arrays, and in previously performed in vitro studies, we demonstrated that SLP from Lactobacillus kefiri CIDCA 8348 (SLP-8348) potentiates the murine macrophage response to LPS in a Ca+2-dependent manner, suggesting the involvement of glycans and their recognition by C-type lectin receptors (CLRs). Therefore, we decided to study the immunogenicity of L. kefiri SLPs and their ability to enhance specific adaptive immunity against other antigens (adjuvant effect), while seeking to understand aspects of the structure that could influence their self-assembly in solution. During the development of the project, we were able to prove that SLPs from three strains of L. kefiri activate antigen-presenting cells and enhance LPS-induced activation through recognition via CLR, resulting in a greater capacity to stimulate antigen-specific LTCD4+. SLP-8321 and SLP- 8348 exert their effect via Mincle, while SLP-5818 does so through SignR3. In vivo studies have also demonstrated the importance of glycan integrity in the immunogenicity and adjuvant capacity of SLP- 8348. By TEM we demonstrated that SLP-8348 adopts a hexagonal geometry upon self-assembly in solution. Therefore, SLPs from L. kefiri emerge as valuable tools for the development of novel vaccine adjuvants from safe bacteria.
Descripción
Palabras clave
Lactobacillus kefiri, vacunas, autoensamblado, receptores de lectina tipo C, vaccines;, self-assembly; C-type lectin receptors
Citación
Bolla, P. A., Malamud, M., Ruggera, J. F. y Serradell, M. Á. (2023). Estudios estructurales y funcionales de proteínas superficiales (capa S) de lactobacilos para su aplicación al desarrollo de nuevos adyuvantes vacunales. Contribuciones de Ciencia y Tecnología, 1(1). https://rid.unaj.edu.ar/handle/123456789/2808