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

Marielle Tamigney Kenfack 1 Marcelina Mazur 2, 1 Teerapat Nualnoi 3, 4 Teresa L Shaffer 5 Abba Ngassimou 1 Yves Blériot 1 Jérôme Marrot 6, 7, 8 Roberta Marchetti 9 Kitisak Sintiprungrat 10 Narisara Chantratita 10, 11 Alba Silipo 9 Antonio Molinaro 9 David P Aucoin 3 Mary N Burtnick 5 Paul J Brett 5 Charles Gauthier 12, 1
1 IC2MP - Institut de Chimie des Milieux et Matériaux de Poitiers
2 Wroclaw University of Environmental and Life Sciences
3 School of Medicine [Reno]
4 PSU - Prince of Songkla University
5 University of South Alabama
6 ILV - Institut Lavoisier de Versailles
7 Université Paris-Saclay
8 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
9 Dipartimento di Scienze Chimiche [Naples]
10 Mahidol University [Bangkok]
11 Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine
12 INRS-IAF - Institut Armand Frappier
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.Melioidosis and glanders are multifaceted infections caused by gram-negative bacteria. Here, the authors synthesize a series of oligosaccharides that mimic the lipopolysaccharides present on the pathogens' surface and use them to develop novel glycoconjugates for vaccine development.
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Submitted on : Tuesday, August 15, 2017 - 8:50:07 PM
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RIIP | CNRS | INRS-IAF | IC2MP | ILV | UNIV-POITIERS | INC-CNRS | UVSQ | INSU | GS-CHIMIE

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Marielle Tamigney Kenfack, Marcelina Mazur, Teerapat Nualnoi, Teresa L Shaffer, Abba Ngassimou, et al.. Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens.. Nature Communications, Nature Publishing Group, 2017, 8 (1), pp.115. ⟨10.1038/s41467-017-00173-8⟩. ⟨pasteur-01574599⟩

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