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Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity
The targeting of immunogens/vaccines to specific immune cells is a promising approach for amplifying immune responses in the absence of exogenous adjuvants. However, the targeting approaches reported thus far require novel, labor-intensive reagents for each vaccine and have primarily been shown as p...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281241/ https://www.ncbi.nlm.nih.gov/pubmed/32422907 http://dx.doi.org/10.3390/pathogens9050375 |
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author | Holland-Tummillo, Kristen M Shoudy, Lauren E Steiner, Donald Kumar, Sudeep Rosa, Sarah J Namjoshi, Prachi Singh, Anju Sellati, Timothy J Gosselin, Edmund J Hazlett, Karsten RO |
author_facet | Holland-Tummillo, Kristen M Shoudy, Lauren E Steiner, Donald Kumar, Sudeep Rosa, Sarah J Namjoshi, Prachi Singh, Anju Sellati, Timothy J Gosselin, Edmund J Hazlett, Karsten RO |
author_sort | Holland-Tummillo, Kristen M |
collection | PubMed |
description | The targeting of immunogens/vaccines to specific immune cells is a promising approach for amplifying immune responses in the absence of exogenous adjuvants. However, the targeting approaches reported thus far require novel, labor-intensive reagents for each vaccine and have primarily been shown as proof-of-concept with isolated proteins and/or inactivated bacteria. We have engineered a plasmid-based, complement receptor-targeting platform that is readily applicable to live forms of multiple gram-negative bacteria, including, but not limited to, Escherichia coli, Klebsiella pneumoniae, and Francisella tularensis. Using F. tularensis as a model, we find that targeted bacteria show increased binding and uptake by macrophages, which coincides with increased p38 and p65 phosphorylation. Mice vaccinated with targeted bacteria produce higher titers of specific antibody that recognizes a greater diversity of bacterial antigens. Following challenge with homologous or heterologous isolates, these mice exhibited less weight loss and/or accelerated weight recovery as compared to counterparts vaccinated with non-targeted immunogens. Collectively, these findings provide proof-of-concept for plasmid-based, complement receptor-targeting of live gram-negative bacteria. |
format | Online Article Text |
id | pubmed-7281241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72812412020-06-15 Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity Holland-Tummillo, Kristen M Shoudy, Lauren E Steiner, Donald Kumar, Sudeep Rosa, Sarah J Namjoshi, Prachi Singh, Anju Sellati, Timothy J Gosselin, Edmund J Hazlett, Karsten RO Pathogens Article The targeting of immunogens/vaccines to specific immune cells is a promising approach for amplifying immune responses in the absence of exogenous adjuvants. However, the targeting approaches reported thus far require novel, labor-intensive reagents for each vaccine and have primarily been shown as proof-of-concept with isolated proteins and/or inactivated bacteria. We have engineered a plasmid-based, complement receptor-targeting platform that is readily applicable to live forms of multiple gram-negative bacteria, including, but not limited to, Escherichia coli, Klebsiella pneumoniae, and Francisella tularensis. Using F. tularensis as a model, we find that targeted bacteria show increased binding and uptake by macrophages, which coincides with increased p38 and p65 phosphorylation. Mice vaccinated with targeted bacteria produce higher titers of specific antibody that recognizes a greater diversity of bacterial antigens. Following challenge with homologous or heterologous isolates, these mice exhibited less weight loss and/or accelerated weight recovery as compared to counterparts vaccinated with non-targeted immunogens. Collectively, these findings provide proof-of-concept for plasmid-based, complement receptor-targeting of live gram-negative bacteria. MDPI 2020-05-14 /pmc/articles/PMC7281241/ /pubmed/32422907 http://dx.doi.org/10.3390/pathogens9050375 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Holland-Tummillo, Kristen M Shoudy, Lauren E Steiner, Donald Kumar, Sudeep Rosa, Sarah J Namjoshi, Prachi Singh, Anju Sellati, Timothy J Gosselin, Edmund J Hazlett, Karsten RO Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity |
title | Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity |
title_full | Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity |
title_fullStr | Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity |
title_full_unstemmed | Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity |
title_short | Autotransporter-Mediated Display of Complement Receptor Ligands by Gram-Negative Bacteria Increases Antibody Responses and Limits Disease Severity |
title_sort | autotransporter-mediated display of complement receptor ligands by gram-negative bacteria increases antibody responses and limits disease severity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281241/ https://www.ncbi.nlm.nih.gov/pubmed/32422907 http://dx.doi.org/10.3390/pathogens9050375 |
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