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.

Development of an immunoblotting assay for serodiagnosis of Burkholderia mallei infection: the whole-cell proteome-based paradigm

“…On the other hand, the LPS is a nonspecific antigen having common epitopes in many Gram-negative bacteria (16). B. mallei and B. pseudomallei have high cross-reactive epitopes in their LPS underlying false positive results in serodiagnosis (22). We assume the whole specific protein antigens assayed by the Western blot can detect the B. mallei -specific epitopes as well as genus-specific epitopes.…”

Immune Control of Burkholderia pseudomallei––Common, High-Frequency T-Cell Responses to a Broad Repertoire of Immunoprevalent Epitopes

“…In recent years, there have been substantial efforts to identify key Bp antigens as vaccine candidates, most commonly through analyzing protective vaccination of mice from acute Bp infection ( 32 – 40 ). This screening strategy has offered a relatively large number of potential immunogens.…”

Recent Advances in the Chemistry of Glycoconjugate Amphiphiles

“…The role of synthetic carbohydrate chemistry for designing and synthesizing carbohydrate derivatives featuring biological properties can be illustrated in the context of vaccines with two recent reports. In a recent publication Gauthier et al hypothesized that the chemical modification of lipopolysaccharide (LPS)-based vaccines antigen could have a strong impact on immune responses [ 112 ]. To validate this hypothesis they prepared several oligosaccharides with the aim of deciphering the immunogenic epitopes of surface polysaccharides.…”