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Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model

Rotaviruses are the primary cause of acute gastroenteritis in children worldwide. Although the implementation of live attenuated vaccines has reduced the number of rotavirus-associated deaths, variance in their effectiveness has been reported in different countries. This fact, among other concerns,...

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Autores principales: Temprana, C. Facundo, Argüelles, Marcelo H., Gutierrez, Nicolás M., Barril, Patricia A., Esteban, Laura E., Silvestre, Dalila, Mandile, Marcelo G., Glikmann, Graciela, Castello, Alejandro A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128627/
https://www.ncbi.nlm.nih.gov/pubmed/30192869
http://dx.doi.org/10.1371/journal.pone.0203700
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author Temprana, C. Facundo
Argüelles, Marcelo H.
Gutierrez, Nicolás M.
Barril, Patricia A.
Esteban, Laura E.
Silvestre, Dalila
Mandile, Marcelo G.
Glikmann, Graciela
Castello, Alejandro A.
author_facet Temprana, C. Facundo
Argüelles, Marcelo H.
Gutierrez, Nicolás M.
Barril, Patricia A.
Esteban, Laura E.
Silvestre, Dalila
Mandile, Marcelo G.
Glikmann, Graciela
Castello, Alejandro A.
author_sort Temprana, C. Facundo
collection PubMed
description Rotaviruses are the primary cause of acute gastroenteritis in children worldwide. Although the implementation of live attenuated vaccines has reduced the number of rotavirus-associated deaths, variance in their effectiveness has been reported in different countries. This fact, among other concerns, leads to continuous efforts for the development of new generation of vaccines against rotavirus.In this work, we describe the obtention of cell wall-derived particles from a recombinant Lactococcus lactis expressing a cell wall-anchored version of the rotavirus VP6 protein. After confirming by SDS-PAGE, Western blot, flow cytometry and electronic immunomicroscopy that these particles were carrying the VP6 protein, their immunogenic potential was evaluated in adult BALB/c mice. For that, mucosal immunizations (oral or intranasal), with or without the dmLT [(double mutant Escherichia coli heat labile toxin LT(R192G/L211A)] adjuvant were performed. The results showed that these cell wall-derived particles were able to generate anti-rotavirus IgG and IgA antibodies only when administered intranasally, whether the adjuvant was present or not. However, the presence of dmLT was necessary to confer protection against rotavirus infection, which was evidenced by a 79.5 percent viral shedding reduction.In summary, this work describes the production of cell wall-derived particles which were able to induce a protective immune response after intranasal immunization. Further studies are needed to characterize the immune response elicited by these particles as well as to determine their potential as an alternative to the use of live L. lactis for mucosal antigen delivery.
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spelling pubmed-61286272018-09-15 Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model Temprana, C. Facundo Argüelles, Marcelo H. Gutierrez, Nicolás M. Barril, Patricia A. Esteban, Laura E. Silvestre, Dalila Mandile, Marcelo G. Glikmann, Graciela Castello, Alejandro A. PLoS One Research Article Rotaviruses are the primary cause of acute gastroenteritis in children worldwide. Although the implementation of live attenuated vaccines has reduced the number of rotavirus-associated deaths, variance in their effectiveness has been reported in different countries. This fact, among other concerns, leads to continuous efforts for the development of new generation of vaccines against rotavirus.In this work, we describe the obtention of cell wall-derived particles from a recombinant Lactococcus lactis expressing a cell wall-anchored version of the rotavirus VP6 protein. After confirming by SDS-PAGE, Western blot, flow cytometry and electronic immunomicroscopy that these particles were carrying the VP6 protein, their immunogenic potential was evaluated in adult BALB/c mice. For that, mucosal immunizations (oral or intranasal), with or without the dmLT [(double mutant Escherichia coli heat labile toxin LT(R192G/L211A)] adjuvant were performed. The results showed that these cell wall-derived particles were able to generate anti-rotavirus IgG and IgA antibodies only when administered intranasally, whether the adjuvant was present or not. However, the presence of dmLT was necessary to confer protection against rotavirus infection, which was evidenced by a 79.5 percent viral shedding reduction.In summary, this work describes the production of cell wall-derived particles which were able to induce a protective immune response after intranasal immunization. Further studies are needed to characterize the immune response elicited by these particles as well as to determine their potential as an alternative to the use of live L. lactis for mucosal antigen delivery. Public Library of Science 2018-09-07 /pmc/articles/PMC6128627/ /pubmed/30192869 http://dx.doi.org/10.1371/journal.pone.0203700 Text en © 2018 Temprana 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
Temprana, C. Facundo
Argüelles, Marcelo H.
Gutierrez, Nicolás M.
Barril, Patricia A.
Esteban, Laura E.
Silvestre, Dalila
Mandile, Marcelo G.
Glikmann, Graciela
Castello, Alejandro A.
Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model
title Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model
title_full Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model
title_fullStr Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model
title_full_unstemmed Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model
title_short Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model
title_sort rotavirus vp6 protein mucosally delivered by cell wall-derived particles from lactococcus lactis induces protection against infection in a murine model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128627/
https://www.ncbi.nlm.nih.gov/pubmed/30192869
http://dx.doi.org/10.1371/journal.pone.0203700
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