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Title: Development of capsular polysaccharide-based glycoconjugates for immunization against melioidosis and glanders

Journal Article · · Frontiers in Cellular and Infection Microbiology
 [1];  [2];  [1];  [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. Colorado State Univ., Fort Collins, CO (United States). Dept. of Microbiology, Immunology and Pathology

Burkholderia pseudomallei and Burkholderia mallei, the etiologic agents of melioidosis and glanders, respectively, cause severe disease in humans and animals and are considered potential agents of biological warfare and terrorism. Diagnosis and treatment of infections caused by these pathogens can be challenging and, in the absence of chemotherapeutic intervention, acute disease is frequently fatal. At present, there are no human or veterinary vaccines available for immunization against these emerging/re-emerging infectious diseases. One of the long term objectives of our research, therefore, is to identify and characterize protective antigens expressed by B. pseudomallei and B. mallei and use them to develop efficacious vaccine candidates. Previous studies have demonstrated that the 6-deoxy-heptan capsular polysaccharide (CPS) expressed by these bacterial pathogens is both a virulence determinant and a protective antigen. Consequently, this carbohydrate moiety has become an important component of the various subunit vaccines that we are currently developing in our laboratory. In the present study, we describe a reliable method for isolating CPS antigens from O-polysaccharide (OPS) deficient strains of B. pseudomallei; including a derivative of the select agent excluded strain Bp82. Utilizing these purified CPS samples, we also describe a simple procedure for covalently linking these T-cell independent antigens to carrier proteins. In addition, we demonstrate that high titer IgG responses can be raised against the CPS component of such constructs. Collectively, these approaches provide a tangible starting point for the development of novel CPS-based glycoconjugates for immunization against melioidosis and 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:
1628031
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

References (48)

Identification of a Burkholderia mallei polysaccharide gene cluster by subtractive hybridization and demonstration that the encoded capsule is an essential virulence determinant journal May 2001
Immunology of bacterial polysaccharide antigens journal November 2003
Structural analysis of capsular polysaccharides expressed by Burkholderia mallei and Burkholderia pseudomallei journal February 2012
Progress toward development of vaccines against melioidosis: A review journal August 2010
An allelic exchange system for compliant genetic manipulation of the select agents Burkholderia pseudomallei and Burkholderia mallei journal February 2009
Aerogenic vaccination with a Burkholderia mallei auxotroph protects against aerosol-initiated glanders in mice journal March 2005
Interleukin-12 induces a Th1-like response to Burkholderia mallei and limited protection in BALB/c mice journal February 2006
Protective efficacy of heat-inactivated B. thailandensis, B. mallei or B. pseudomallei against experimental melioidosis and glanders journal July 2009
Melioidosis journal May 2003
Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei journal April 2006
Relationship Between Antigenicity and Pathogenicity forBurkholderia pseudomalleiandBurkholderia malleiRevealed by a Large Panel of Mouse MAbs journal August 2008
Clinical Features and Epidemiology of Melioidosis Pneumonia: Results From a 21-Year Study and Review of the Literature journal November 2011
Note: Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei-like species journal January 1998
Passive protection against Burkholderia pseudomallei infection in mice by monoclonal antibodies against capsular polysaccharide, lipopolysaccharide or proteins journal December 2002
A Comparative Study of Pseudomonas pseudomallei and Bacillus mallei journal May 1966
Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis journal December 2004
Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis journal August 2004
Proposal of Burkholderia gen. nov. and Transfer of Seven Species of the Genus Pseudomonas Homology Group II to the New Genus, with the Type Species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov. journal December 1992
Glanders: off to the races with Burkholderia mallei journal December 2007
Efflux-Mediated Aminoglycoside and Macrolide Resistance in Burkholderia pseudomallei journal March 1999
In Vitro and In Vivo Studies of Monoclonal Antibodies with Prominent Bactericidal Activity against Burkholderia pseudomallei and Burkholderia mallei journal March 2011
Burkholderia thailandensis oacA Mutants Facilitate the Expression of Burkholderia mallei -Like O Polysaccharides journal November 2010
The Cluster 1 Type VI Secretion System Is a Major Virulence Determinant in Burkholderia pseudomallei journal February 2011
A Burkholderia pseudomallei ΔpurM Mutant Is Avirulent in Immunocompetent and Immunodeficient Animals: Candidate Strain for Exclusion from Select-Agent Lists journal April 2010
The Burkholderia pseudomallei Δ asd Mutant Exhibits Attenuated Intracellular Infectivity and Imparts Protection against Acute Inhalation Melioidosis in Mice journal October 2011
Engineering and Preclinical Evaluation of Attenuated Nontyphoidal Salmonella Strains Serving as Live Oral Vaccines and as Reagent Strains journal October 2011
Salmonella enterica Serovar Enteritidis Core O Polysaccharide Conjugated to H:g,m Flagellin as a Candidate Vaccine for Protection against Invasive Infection with S. Enteritidis journal October 2011
Structural characterization of the lipopolysaccharide O antigens of Burkholderia pseudomallei. journal January 1995
Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates. journal January 1996
Detection of Bacterial Virulence Genes by Subtractive Hybridization: Identification of Capsular Polysaccharide ofBurkholderia pseudomallei as a Major Virulence Determinant journal January 2001
NonviableBurkholderia malleiInduces a Mixed Th1- and Th2-Like Cytokine Response in BALB/c Mice journal May 2002
A Mutant ofBurkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis journal September 2002
The Capsular Polysaccharide ofBurkholderia pseudomalleiContributes to Survival in Serum by Reducing Complement Factor C3b Deposition journal February 2005
Mutagenesis of Burkholderia pseudomallei with Tn5-OT182: isolation of motility mutants and molecular characterization of the flagellin structural gene journal April 1997
Identification of Circulating Bacterial Antigens by In Vivo Microbial Antigen Discovery journal September 2011
Molecular Insights into Burkholderia pseudomallei and Burkholderia mallei Pathogenesis journal October 2010
Host immunity in the protective response to vaccination with heat-killed Burkholderia mallei journal September 2008
Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates journal January 2010
Melioidosis Vaccines: A Systematic Review and Appraisal of the Potential to Exploit Biodefense Vaccines for Public Health Purposes journal January 2012
Polysaccharide Specific Monoclonal Antibodies Provide Passive Protection against Intranasal Challenge with Burkholderia pseudomallei journal April 2012
Conjugate vaccines journal October 2003
Strategies toward vaccines against Burkholderia mallei and Burkholderia pseudomallei journal November 2008
Vaccines based on the cell surface carbohydrates of pathogenic bacteria journal June 2005
Carbohydrate Based Vaccines journal June 2000
Vaccines Against Polysaccharide Antigens journal November 2001
Public Health Assessment of Potential Biological Terrorism Agents journal February 2002
Melioidosis in Animals, Thailand, 2006–2010 journal February 2012
Human Glanders: Report of Six Cases journal January 1947

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Burkholderia pseudomallei Capsular Polysaccharide Conjugates Provide Protection against Acute Melioidosis journal May 2014
Impact of Binge Alcohol Intoxication on the Humoral Immune Response during Burkholderia spp. Infections journal May 2019
Structural characterisation of the capsular polysaccharide expressed by Burkholderia thailandensis strain E555:: wbiI (pKnock-KmR) and assessment of the significance of the 2-O-acetyl group in immune protection journal November 2017
The autotransporter protein BatA is a protective antigen against lethal aerosol infection with Burkholderia mallei and Burkholderia pseudomallei journal April 2019
Development of Rapid Enzyme-Linked Immunosorbent Assays for Detection of Antibodies to Burkholderia pseudomallei journal February 2016
An avirulent Burkholderia pseudomallei ∆purM strain with atypical type B LPS: expansion of the toolkit for biosafe studies of melioidosis journal June 2017
In vivo Distribution and Clearance of Purified Capsular Polysaccharide from Burkholderia pseudomallei in a Murine Model journal December 2016
Comparison of O-polysaccharide and hemolysin co-regulated protein as target antigens for serodiagnosis of melioidosis journal March 2017
Genome-scale analysis of the genes that contribute to Burkholderia pseudomallei biofilm formation identifies a crucial exopolysaccharide biosynthesis gene cluster journal June 2017
Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice journal October 2013
Zoonotic Pathogens Transmitted from Equines: Diagnosis and Control journal January 2015
Outer Membrane Vesicle Vaccines from Biosafe Surrogates Prevent Acute Lethal Glanders in Mice journal January 2018
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