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Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles

Recombinant subunit vaccine engineering increasingly focuses on the development of more effective delivery platforms. However, current recombinant vaccines fail to sufficiently stimulate protective adaptive immunity against a wide range of pathogens while remaining a cost effective solution to globa...

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Autores principales: Rosenthal, Joseph A., Huang, Chung-Jr., Doody, Anne M., Leung, Tiffany, Mineta, Kaho, Feng, Danielle D., Wayne, Elizabeth C., Nishimura, Nozomi, Leifer, Cynthia, DeLisa, Matthew P., Mendez, Susana, Putnam, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245113/
https://www.ncbi.nlm.nih.gov/pubmed/25426709
http://dx.doi.org/10.1371/journal.pone.0112802
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author Rosenthal, Joseph A.
Huang, Chung-Jr.
Doody, Anne M.
Leung, Tiffany
Mineta, Kaho
Feng, Danielle D.
Wayne, Elizabeth C.
Nishimura, Nozomi
Leifer, Cynthia
DeLisa, Matthew P.
Mendez, Susana
Putnam, David
author_facet Rosenthal, Joseph A.
Huang, Chung-Jr.
Doody, Anne M.
Leung, Tiffany
Mineta, Kaho
Feng, Danielle D.
Wayne, Elizabeth C.
Nishimura, Nozomi
Leifer, Cynthia
DeLisa, Matthew P.
Mendez, Susana
Putnam, David
author_sort Rosenthal, Joseph A.
collection PubMed
description Recombinant subunit vaccine engineering increasingly focuses on the development of more effective delivery platforms. However, current recombinant vaccines fail to sufficiently stimulate protective adaptive immunity against a wide range of pathogens while remaining a cost effective solution to global health challenges. Taking an unorthodox approach to this fundamental immunological challenge, we isolated the TLR-targeting capability of the probiotic E. coli Nissle 1917 bacteria (EcN) by engineering bionanoparticlate antigen carriers derived from EcN outer membrane vesicles (OMVs). Exogenous model antigens expressed by these modified bacteria as protein fusions with the bacterial enterotoxin ClyA resulted in their display on the surface of the carrier OMVs. Vaccination with the engineered EcN OMVs in a BALB/c mouse model, and subsequent mechanism of action analysis, established the EcN OMV’s ability to induce self-adjuvanted robust and protective humoral and T(H)1-biased cellular immunity to model antigens. This finding appears to be strain-dependent, as OMV antigen carriers similarly engineered from a standard K12 E. coli strain derivative failed to generate a comparably robust antigen-specific T(H)1 bias. The results demonstrate that unlike traditional subunit vaccines, these biomolecularly engineered “pathogen-like particles” derived from traditionally overlooked, naturally potent immunomodulators have the potential to effectively couple recombinant antigens with meaningful immunity in a broadly applicable fashion.
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spelling pubmed-42451132014-12-05 Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles Rosenthal, Joseph A. Huang, Chung-Jr. Doody, Anne M. Leung, Tiffany Mineta, Kaho Feng, Danielle D. Wayne, Elizabeth C. Nishimura, Nozomi Leifer, Cynthia DeLisa, Matthew P. Mendez, Susana Putnam, David PLoS One Research Article Recombinant subunit vaccine engineering increasingly focuses on the development of more effective delivery platforms. However, current recombinant vaccines fail to sufficiently stimulate protective adaptive immunity against a wide range of pathogens while remaining a cost effective solution to global health challenges. Taking an unorthodox approach to this fundamental immunological challenge, we isolated the TLR-targeting capability of the probiotic E. coli Nissle 1917 bacteria (EcN) by engineering bionanoparticlate antigen carriers derived from EcN outer membrane vesicles (OMVs). Exogenous model antigens expressed by these modified bacteria as protein fusions with the bacterial enterotoxin ClyA resulted in their display on the surface of the carrier OMVs. Vaccination with the engineered EcN OMVs in a BALB/c mouse model, and subsequent mechanism of action analysis, established the EcN OMV’s ability to induce self-adjuvanted robust and protective humoral and T(H)1-biased cellular immunity to model antigens. This finding appears to be strain-dependent, as OMV antigen carriers similarly engineered from a standard K12 E. coli strain derivative failed to generate a comparably robust antigen-specific T(H)1 bias. The results demonstrate that unlike traditional subunit vaccines, these biomolecularly engineered “pathogen-like particles” derived from traditionally overlooked, naturally potent immunomodulators have the potential to effectively couple recombinant antigens with meaningful immunity in a broadly applicable fashion. Public Library of Science 2014-11-26 /pmc/articles/PMC4245113/ /pubmed/25426709 http://dx.doi.org/10.1371/journal.pone.0112802 Text en © 2014 Rosenthal 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rosenthal, Joseph A.
Huang, Chung-Jr.
Doody, Anne M.
Leung, Tiffany
Mineta, Kaho
Feng, Danielle D.
Wayne, Elizabeth C.
Nishimura, Nozomi
Leifer, Cynthia
DeLisa, Matthew P.
Mendez, Susana
Putnam, David
Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles
title Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles
title_full Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles
title_fullStr Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles
title_full_unstemmed Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles
title_short Mechanistic Insight into the T(H)1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles
title_sort mechanistic insight into the t(h)1-biased immune response to recombinant subunit vaccines delivered by probiotic bacteria-derived outer membrane vesicles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245113/
https://www.ncbi.nlm.nih.gov/pubmed/25426709
http://dx.doi.org/10.1371/journal.pone.0112802
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