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Title: Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens

Abstract

Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs). Our approach is based on the conversion of an L-rhamnose into a 6-deoxy-L-talose residue at a late stage of the synthetic sequence. Using biochemical and biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific monoclonal antibodies with terminal OAg residues. Mice immunized with terminal disaccharide–CRM197 constructs produced high-titer antibody responses that crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation for the development of novel therapeutics, diagnostics, and vaccine candidates to combat diseases caused by Bp and Bm.

Authors:
 [1];  [2];  [3];  [4];  [1];  [1];  [5];  [6];  [7];  [7];  [6];  [6];  [8];  [4];  [4];  [9]
  1. Université de Poitiers (France)
  2. Université de Poitiers (France); Wroclaw Univ. of Environmental and Life Sciences (Poland)
  3. Univ. of Nevada School of Medicine, Reno, NV (United States); Prince of Songkla Univ., Songkhla (Thailand)
  4. Univ. of South Alabama, Mobile, AL (United States)
  5. Univ. Paris-Saclay, Versailles (France)
  6. Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, Naples (Italy)
  7. Mahidol Univ., Bangkok (Thailand)
  8. Univ. of Nevada School of Medicine, Reno, NV (United States)
  9. Université de Poitiers (France); Univ. of Quebec, Laval QC (Canada)
Publication Date:
Research Org.:
Univ. of Georgia, Athens, GA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1535102
Grant/Contract Number:  
FG02-93ER20097
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Tamigney Kenfack, Marielle, Mazur, Marcelina, Nualnoi, Teerapat, Shaffer, Teresa L., Ngassimou, Abba, Blériot, Yves, Marrot, Jérôme, Marchetti, Roberta, Sintiprungrat, Kitisak, Chantratita, Narisara, Silipo, Alba, Molinaro, Antonio, AuCoin, David P., Burtnick, Mary N., Brett, Paul J., and Gauthier, Charles. Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens. United States: N. p., 2017. Web. doi:10.1038/s41467-017-00173-8.
Tamigney Kenfack, Marielle, Mazur, Marcelina, Nualnoi, Teerapat, Shaffer, Teresa L., Ngassimou, Abba, Blériot, Yves, Marrot, Jérôme, Marchetti, Roberta, Sintiprungrat, Kitisak, Chantratita, Narisara, Silipo, Alba, Molinaro, Antonio, AuCoin, David P., Burtnick, Mary N., Brett, Paul J., & Gauthier, Charles. Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens. United States. doi:10.1038/s41467-017-00173-8.
Tamigney Kenfack, Marielle, Mazur, Marcelina, Nualnoi, Teerapat, Shaffer, Teresa L., Ngassimou, Abba, Blériot, Yves, Marrot, Jérôme, Marchetti, Roberta, Sintiprungrat, Kitisak, Chantratita, Narisara, Silipo, Alba, Molinaro, Antonio, AuCoin, David P., Burtnick, Mary N., Brett, Paul J., and Gauthier, Charles. Mon . "Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens". United States. doi:10.1038/s41467-017-00173-8. https://www.osti.gov/servlets/purl/1535102.
@article{osti_1535102,
title = {Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens},
author = {Tamigney Kenfack, Marielle and Mazur, Marcelina and Nualnoi, Teerapat and Shaffer, Teresa L. and Ngassimou, Abba and Blériot, Yves and Marrot, Jérôme and Marchetti, Roberta and Sintiprungrat, Kitisak and Chantratita, Narisara and Silipo, Alba and Molinaro, Antonio and AuCoin, David P. and Burtnick, Mary N. and Brett, Paul J. and Gauthier, Charles},
abstractNote = {Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs). Our approach is based on the conversion of an L-rhamnose into a 6-deoxy-L-talose residue at a late stage of the synthetic sequence. Using biochemical and biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific monoclonal antibodies with terminal OAg residues. Mice immunized with terminal disaccharide–CRM197 constructs produced high-titer antibody responses that crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation for the development of novel therapeutics, diagnostics, and vaccine candidates to combat diseases caused by Bp and Bm.},
doi = {10.1038/s41467-017-00173-8},
journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 8,
place = {United States},
year = {2017},
month = {7}
}

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Cited by: 11 works
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    journal, March 2010

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    mAbs to Bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia
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    Facile Synthesis ofα- andβ-O-Glycosyl Imidates; Preparation of Glycosides and Disaccharides
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    • Angewandte Chemie International Edition in English, Vol. 19, Issue 9
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    A gold nanoparticle-linked glycoconjugate vaccine against Burkholderia mallei
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    Polysaccharide Specific Monoclonal Antibodies Provide Passive Protection against Intranasal Challenge with Burkholderia pseudomallei
    journal, April 2012


    The type II O-antigenic polysaccharide moiety of Burkholderia pseudomallei lipopolysaccharide is required for serum resistance and virulence
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    • Silva, Ediane B.; Dow, Steven W.
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    • DOI: 10.3389/fcimb.2013.00010

    Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis
    journal, December 2004


    Rigid conformation of tricyclic orthoesters of sugars
    journal, February 1971


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