Sequence- and Structure-Based Immunoreactive Epitope Discovery for Burkholderia pseudomallei Flagellin

Burkholderia pseudomallei is a Gram-negative bacterium responsible for
melioidosis, a serious and often fatal infectious disease that is poorly
controlled by existing treatments. Due to its inherent resistance to the
major antibiotic classes and its facultative intracellular
pathogenicity, an effective vaccine would be extremely desirable, along
with appropriate prevention and therapeutic management. One of the main
subunit vaccine candidates is flagellin of Burkholderia pseudomallei
(FliC(Bp)). Here, we present the high resolution crystal structure of
FliC(Bp) and report the synthesis and characterization of three peptides
predicted to be both B and T cell FliC(Bp) epitopes, by both
structure-based in silico methods, and sequence-based epitope prediction
tools. All three epitopes were shown to be immunoreactive against human
IgG antibodies and to elicit cytokine production from human peripheral
blood mononuclear cells. Furthermore, two of the peptides (F51-69 and
F270-288) were found to be dominant immunoreactive epitopes, and their
antibodies enhanced the bactericidal activities of purified human
neutrophils. The epitopes derived from this study may represent
potential melioidosis vaccine components.