Browsing by Author "Teresa L. Shaffer"

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    Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens
    (2017-12-01) Marielle Tamigney Kenfack; Marcelina Mazur; Teerapat Nualnoi; Teresa L. Shaffer; Abba Ngassimou; Yves Blériot; Jérôme Marrot; Roberta Marchetti; Kitisak Sintiprungrat; Narisara Chantratita; Alba Silipo; Antonio Molinaro; David P. AuCoin; Mary N. Burtnick; Paul J. Brett; Charles Gauthier; Universite de Poitiers; Uniwersytet Przyrodniczy we Wroclawiu; University of Nevada School of Medicine; Prince of Songkla University; University of South Alabama; Institut Lavoisier de Versailles; Università degli Studi di Napoli Federico II; Mahidol University; INRS-Institut Armand Frappier
    © 2017 The Author(s). 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.