TY - JOUR
T1 - Sequence-and structure-based immunoreactive epitope discovery for Burkholderia pseudomallei flagellin
AU - Nithichanon, Arnone
AU - Rinchai, Darawan
AU - Gori, Alessandro
AU - Lassaux, Patricia
AU - Peri, Claudio
AU - Conchillio-Solé, Oscar
AU - Ferrer-Navarro, Mario
AU - Gourlay, Louise J.
AU - Nardini, Marco
AU - Vila, Jordi
AU - Daura, Xavier
AU - Colombo, Giorgio
AU - Bolognesi, Martino
AU - Lertmemonkolchai, Ganjana
PY - 2015/1/1
Y1 - 2015/1/1
N2 - © 2015 Nithichanon et al. 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 (FliCBp). Here, we present the high resolution crystal structure of FliCBp and report the synthesis and characterization of three peptides predicted to be both B and T cell FliCBp epitopes, by both structure-based in silico methods, and sequencebased 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.
AB - © 2015 Nithichanon et al. 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 (FliCBp). Here, we present the high resolution crystal structure of FliCBp and report the synthesis and characterization of three peptides predicted to be both B and T cell FliCBp epitopes, by both structure-based in silico methods, and sequencebased 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.
U2 - 10.1371/journal.pntd.0003917
DO - 10.1371/journal.pntd.0003917
M3 - Article
SN - 1935-2727
VL - 9
SP - 1
EP - 20
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 7
M1 - A016
ER -