Developing Peptide Mimotopes of Capsular Polysaccharides and Lipopolysaccharides Protective Antigens of Pathogenic Burkholderia Bacteria

Authors

• PF Guo
• J Zhang
• S Tsai
• BJ Li
• SC Lo

Abstract

Background: Burkholderia pseudomallei (BP) and Burkholderia mallei (BM) are the causative agents of melioidosis and glanders, respectively. Effective therapeutics and safe vaccines against these bacterial pathogens are urgently needed. Our lab was previously supported by DTRA/DoD to develop BP and BM-specific monoclonal antibodies (MAbs) and to evaluate their anti-BP and BM effects. After studying more than 100 MAbs developed, we identified 4 MAbs recognizing specifically capsular polysaccharides (PS) or lipopolysaccharides (LPS) of BP and BM possessed the high protective activities against lethal doses of intranasal BP and BM infections in mice. Methods: Using phage display panning against three different phage peptide libraries, we selected phage clones specifically recognized by each of the 4 protective MAbs. Results/Discussion: After examining by sequencing of a total of 240 candidate phage clones, we eventually identified 6 specific clones and their peptide inserts. Chemically synthesized peptides corresponding to those displayed by the 6 phage clones were conjugated to keyhole limpet hemocyanin (KLH) carrier protein and tested for their binding specificity of the respective protective MAbs. The study revealed that 4 of the 6 peptides functioned well as “mimotopes” of Burkholderia PS and LPS as demonstrated a high degree of specific competition against the binding of 3 protective MAbs to BP and BM. Our results suggest that the 4 selected peptide mimics corresponding to PS/LPS protective antigens of BP and BM could potentially be developed into peptide vaccines, when the public is facing un-expected, devastating biothreats of the pathogenic Burkholderia bacteria.

Scientific Focus Area: Microbiology and Infectious Diseases

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