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.

Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens / 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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 8:115:(2017), pp. 1-13. [10.1038/s41467-017-00173-8]

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

MARCHETTI, ROBERTA;SILIPO, ALBA;MOLINARO, ANTONIO;
2017

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.
2017
Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens / 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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 8:115:(2017), pp. 1-13. [10.1038/s41467-017-00173-8]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/681479
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