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

Journal Article · · Frontiers in Cellular and Infection Microbiology
 [1];  [2];  [3];  [2];  [1]
  1. Univ. of South Alabama, Mobile, AL (United States). Dept. of Microbiology and Immunology
  2. Univ. of Georgia, Athens, GA (United States). Complex Carbohydrate Research Center
  3. Univ. of South Alabama, Mobile, AL (United States). Dept. of Comparative Medicine

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.

Research Organization:
Univ. of Georgia, Athens, GA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
FG02-93ER20097; FG05-93ER20097
OSTI ID:
1628032
Journal Information:
Frontiers in Cellular and Infection Microbiology, Vol. 2; ISSN 2235-2988
Publisher:
Frontiers Research FoundationCopyright Statement
Country of Publication:
United States
Language:
English

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Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei journal September 2017
Development of Subunit Vaccines That Provide High-Level Protection and Sterilizing Immunity against Acute Inhalational Melioidosis journal November 2017
Burkholderia pseudomallei Capsular Polysaccharide Conjugates Provide Protection against Acute Melioidosis journal May 2014
Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens journal July 2017
Evaluation of Polysaccharide-Based Latex Agglutination Assays for the Rapid Detection of Antibodies to Burkholderia pseudomallei journal September 2015
Development of Immunoassays for Burkholderia pseudomallei Typical and Atypical Lipopolysaccharide Strain Typing journal December 2016