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Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa
Klebsiella pneumoniae (KP) and Pseudomonas aeruginosa (PA) are important human pathogens that are associated with a range of infection types, including wound and disseminated infections. Treatment has been complicated by rising rates of antimicrobial resistance. Immunoprophylactic strategies are not...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126813/ https://www.ncbi.nlm.nih.gov/pubmed/30188914 http://dx.doi.org/10.1371/journal.pone.0203143 |
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author | Hegerle, Nicolas Choi, Myeongjin Sinclair, James Amin, Mohammed N. Ollivault-Shiflett, Morgane Curtis, Brittany Laufer, Rachel S. Shridhar, Surekha Brammer, Jerod Toapanta, Franklin R. Holder, Ian Alan Pasetti, Marcela F. Lees, Andrew Tennant, Sharon M. Cross, Alan S. Simon, Raphael |
author_facet | Hegerle, Nicolas Choi, Myeongjin Sinclair, James Amin, Mohammed N. Ollivault-Shiflett, Morgane Curtis, Brittany Laufer, Rachel S. Shridhar, Surekha Brammer, Jerod Toapanta, Franklin R. Holder, Ian Alan Pasetti, Marcela F. Lees, Andrew Tennant, Sharon M. Cross, Alan S. Simon, Raphael |
author_sort | Hegerle, Nicolas |
collection | PubMed |
description | Klebsiella pneumoniae (KP) and Pseudomonas aeruginosa (PA) are important human pathogens that are associated with a range of infection types, including wound and disseminated infections. Treatment has been complicated by rising rates of antimicrobial resistance. Immunoprophylactic strategies are not constrained by antimicrobial resistance mechanisms. Vaccines against these organisms would be important public health tools, yet they are not available. KP surface O polysaccharides (OPS) are protective antigens in animal models of infection. Similarly, PA flagellin (Fla), the major subunit of the flagellar filament, is required for virulence and is a target of protective antibodies in animal models. We report herein the development of a combined KP and PA glycoconjugate vaccine comprised of the four most common KP OPS types associated with human infections (O1, O2, O3, O5), chemically linked to the two Fla types of PA (FlaA, FlaB). Conjugation of KP OPS to PA Fla enhanced anti-polysaccharide immune responses and produced a formulation that generated antibody titers to the four KP OPS types and both PA Fla antigens in rabbits. Passive transfer of vaccine-induced rabbit antisera reduced the bacterial burden and protected mice against fatal intravenous KP infection. Mice passively transferred with conjugate-induced antisera were also protected against PA infection after thermal injury with a FlaB-expressing isolate, but not a FlaA isolate. Taken together, these promising preclinical results provide important proof-of-concept for a broad spectrum human vaccine to prevent KP and PA infections. |
format | Online Article Text |
id | pubmed-6126813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61268132018-09-15 Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa Hegerle, Nicolas Choi, Myeongjin Sinclair, James Amin, Mohammed N. Ollivault-Shiflett, Morgane Curtis, Brittany Laufer, Rachel S. Shridhar, Surekha Brammer, Jerod Toapanta, Franklin R. Holder, Ian Alan Pasetti, Marcela F. Lees, Andrew Tennant, Sharon M. Cross, Alan S. Simon, Raphael PLoS One Research Article Klebsiella pneumoniae (KP) and Pseudomonas aeruginosa (PA) are important human pathogens that are associated with a range of infection types, including wound and disseminated infections. Treatment has been complicated by rising rates of antimicrobial resistance. Immunoprophylactic strategies are not constrained by antimicrobial resistance mechanisms. Vaccines against these organisms would be important public health tools, yet they are not available. KP surface O polysaccharides (OPS) are protective antigens in animal models of infection. Similarly, PA flagellin (Fla), the major subunit of the flagellar filament, is required for virulence and is a target of protective antibodies in animal models. We report herein the development of a combined KP and PA glycoconjugate vaccine comprised of the four most common KP OPS types associated with human infections (O1, O2, O3, O5), chemically linked to the two Fla types of PA (FlaA, FlaB). Conjugation of KP OPS to PA Fla enhanced anti-polysaccharide immune responses and produced a formulation that generated antibody titers to the four KP OPS types and both PA Fla antigens in rabbits. Passive transfer of vaccine-induced rabbit antisera reduced the bacterial burden and protected mice against fatal intravenous KP infection. Mice passively transferred with conjugate-induced antisera were also protected against PA infection after thermal injury with a FlaB-expressing isolate, but not a FlaA isolate. Taken together, these promising preclinical results provide important proof-of-concept for a broad spectrum human vaccine to prevent KP and PA infections. Public Library of Science 2018-09-06 /pmc/articles/PMC6126813/ /pubmed/30188914 http://dx.doi.org/10.1371/journal.pone.0203143 Text en © 2018 Hegerle 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 Hegerle, Nicolas Choi, Myeongjin Sinclair, James Amin, Mohammed N. Ollivault-Shiflett, Morgane Curtis, Brittany Laufer, Rachel S. Shridhar, Surekha Brammer, Jerod Toapanta, Franklin R. Holder, Ian Alan Pasetti, Marcela F. Lees, Andrew Tennant, Sharon M. Cross, Alan S. Simon, Raphael Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa |
title | Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa |
title_full | Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa |
title_fullStr | Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa |
title_full_unstemmed | Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa |
title_short | Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa |
title_sort | development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with klebsiella pneumoniae and pseudomonas aeruginosa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126813/ https://www.ncbi.nlm.nih.gov/pubmed/30188914 http://dx.doi.org/10.1371/journal.pone.0203143 |
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