Development of novel O-polysaccharide based glycoconjugates for immunization against glanders

Burkholderia mallei the etiologic agent of glanders, causes severe disease in humans and animals and is a potential agent of biological warfare and terrorism. Diagnosis and treatment of glanders can be challenging, and in the absence of chemotherapeutic intervention, acute human disease is invariabl...

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Main Authors:	Burtnick, Mary N., Heiss, Christian, Schuler, A. Michele, Azadi, Parastoo, Brett, Paul J.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506924/

id	pubmed-3506924
recordtype	oai_dc
spelling	pubmed-35069242012-11-30 Development of novel O-polysaccharide based glycoconjugates for immunization against glanders Burtnick, Mary N. Heiss, Christian Schuler, A. Michele Azadi, Parastoo Brett, Paul J. Microbiology Burkholderia mallei the etiologic agent of glanders, causes severe disease in humans and animals and is a potential agent of biological warfare and terrorism. Diagnosis and treatment of glanders can be challenging, and in the absence of chemotherapeutic intervention, acute human disease is invariably fatal. At present, there are no human or veterinary vaccines available for immunization against disease. One of the goals of our research, therefore, is to identify and characterize protective antigens expressed by B. mallei and use them to develop efficacious glanders vaccine candidates. Previous studies have demonstrated that the O-polysaccharide (OPS) expressed by B. mallei is both a virulence factor and a protective antigen. Recently, we demonstrated that Burkholderia thailandensis, a closely related but non-pathogenic species, can be genetically manipulated to express OPS antigens that are recognized by B. mallei OPS-specific monoclonal antibodies (mAbs). As a result, these antigens have become important components of the various OPS-based subunit vaccines that we are currently developing in our laboratory. In this study, we describe a method for isolating B. mallei-like OPS antigens from B. thailandensis oacA mutants. Utilizing these purified OPS antigens, we also describe a simple procedure for coupling the polysaccharides to protein carriers such as cationized bovine serum albumin, diphtheria toxin mutant CRM197 and cholera toxin B subunit. Additionally, we demonstrate that high titer IgG responses against purified B. mallei LPS can be generated by immunizing mice with the resulting constructs. Collectively, these approaches provide a rational starting point for the development of novel OPS-based glycoconjugates for immunization against glanders. Frontiers Media S.A. 2012-11-27 /pmc/articles/PMC3506924/ /pubmed/23205347 http://dx.doi.org/10.3389/fcimb.2012.00148 Text en Copyright © 2012 Burtnick, Heiss, Schuler, Azadi and Brett. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Burtnick, Mary N. Heiss, Christian Schuler, A. Michele Azadi, Parastoo Brett, Paul J.
spellingShingle	Burtnick, Mary N. Heiss, Christian Schuler, A. Michele Azadi, Parastoo Brett, Paul J. Development of novel O-polysaccharide based glycoconjugates for immunization against glanders
author_facet	Burtnick, Mary N. Heiss, Christian Schuler, A. Michele Azadi, Parastoo Brett, Paul J.
author_sort	Burtnick, Mary N.
title	Development of novel O-polysaccharide based glycoconjugates for immunization against glanders
title_short	Development of novel O-polysaccharide based glycoconjugates for immunization against glanders
title_full	Development of novel O-polysaccharide based glycoconjugates for immunization against glanders
title_fullStr	Development of novel O-polysaccharide based glycoconjugates for immunization against glanders
title_full_unstemmed	Development of novel O-polysaccharide based glycoconjugates for immunization against glanders
title_sort	development of novel o-polysaccharide based glycoconjugates for immunization against glanders
description	Burkholderia mallei the etiologic agent of glanders, causes severe disease in humans and animals and is a potential agent of biological warfare and terrorism. Diagnosis and treatment of glanders can be challenging, and in the absence of chemotherapeutic intervention, acute human disease is invariably fatal. At present, there are no human or veterinary vaccines available for immunization against disease. One of the goals of our research, therefore, is to identify and characterize protective antigens expressed by B. mallei and use them to develop efficacious glanders vaccine candidates. Previous studies have demonstrated that the O-polysaccharide (OPS) expressed by B. mallei is both a virulence factor and a protective antigen. Recently, we demonstrated that Burkholderia thailandensis, a closely related but non-pathogenic species, can be genetically manipulated to express OPS antigens that are recognized by B. mallei OPS-specific monoclonal antibodies (mAbs). As a result, these antigens have become important components of the various OPS-based subunit vaccines that we are currently developing in our laboratory. In this study, we describe a method for isolating B. mallei-like OPS antigens from B. thailandensis oacA mutants. Utilizing these purified OPS antigens, we also describe a simple procedure for coupling the polysaccharides to protein carriers such as cationized bovine serum albumin, diphtheria toxin mutant CRM197 and cholera toxin B subunit. Additionally, we demonstrate that high titer IgG responses against purified B. mallei LPS can be generated by immunizing mice with the resulting constructs. Collectively, these approaches provide a rational starting point for the development of novel OPS-based glycoconjugates for immunization against glanders.
publisher	Frontiers Media S.A.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506924/
_version_	1611935531053088768

Development of novel O-polysaccharide based glycoconjugates for immunization against glanders

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