TY - JOUR
T1 - NHP BurkPx
T2 - A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates
AU - Celona, Kimberly R.
AU - Shannon, Austin B.
AU - Sonderegger, Derek
AU - Yi, Jinhee
AU - Monroy, Fernando P.
AU - Allender, Christopher
AU - Hornstra, Heidie
AU - Barnes, Mary B.
AU - Didier, Elizabeth S.
AU - Bohm, Rudolf P.
AU - Phillippi-Falkenstein, Kathrine
AU - Sanford, Daniel
AU - Keim, Paul
AU - Settles, Erik W.
N1 - Publisher Copyright:
© 2023 Celona et al.
PY - 2023/2/8
Y1 - 2023/2/8
N2 - Background Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by culturing B. pseudomallei, and there are no standardized detection protocols for NHP. NHP are an important animal model for melioidosis research including clinical trials and development of biodefense countermeasures. Methodology/Principle findings We evaluated the diagnostic potential of the multiple antigen serological assay, BurkPx, in NHP using two sera sets: (i) 115 B. pseudomallei-challenged serum samples from 80 NHP collected each week post-exposure (n = 52) and at euthanasia (n = 47), and (ii) 126 B. pseu-domallei-naïve/negative serum samples. We observed early IgM antibody responses to car-bohydrate antigens followed by IgG antibody recognition to multiple B. pseudomallei protein antigens during the second week of infection. B. pseudomallei negative serum samples had low to intermediate antibody cross reactivity to the antigens in this assay. Infection time was predicted as the determining factor in the variation of antibody responses, with 77.67% of variation explained by the first component of the principal component analysis. A multiple antigen model generated a binary prediction metric (^p), which when applied to all data resulted in 100% specificity and 63.48% sensitivity. Removal of week 1 B. pseudomallei challenged serum samples increased the sensitivity of the model to 95%. Conclusion/Significance We employed a previously standardized assay for humans, the BurkPx assay, and assessed its diagnostic potential for detection of B. pseudomallei exposure in NHP. The assay is expected to be useful for surveillance in NHP colonies, in investigations of sus-pected accidental releases or exposures, and for identifying vaccine correlates of protection.
AB - Background Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by culturing B. pseudomallei, and there are no standardized detection protocols for NHP. NHP are an important animal model for melioidosis research including clinical trials and development of biodefense countermeasures. Methodology/Principle findings We evaluated the diagnostic potential of the multiple antigen serological assay, BurkPx, in NHP using two sera sets: (i) 115 B. pseudomallei-challenged serum samples from 80 NHP collected each week post-exposure (n = 52) and at euthanasia (n = 47), and (ii) 126 B. pseu-domallei-naïve/negative serum samples. We observed early IgM antibody responses to car-bohydrate antigens followed by IgG antibody recognition to multiple B. pseudomallei protein antigens during the second week of infection. B. pseudomallei negative serum samples had low to intermediate antibody cross reactivity to the antigens in this assay. Infection time was predicted as the determining factor in the variation of antibody responses, with 77.67% of variation explained by the first component of the principal component analysis. A multiple antigen model generated a binary prediction metric (^p), which when applied to all data resulted in 100% specificity and 63.48% sensitivity. Removal of week 1 B. pseudomallei challenged serum samples increased the sensitivity of the model to 95%. Conclusion/Significance We employed a previously standardized assay for humans, the BurkPx assay, and assessed its diagnostic potential for detection of B. pseudomallei exposure in NHP. The assay is expected to be useful for surveillance in NHP colonies, in investigations of sus-pected accidental releases or exposures, and for identifying vaccine correlates of protection.
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U2 - 10.1371/journal.pntd.0011067
DO - 10.1371/journal.pntd.0011067
M3 - Article
C2 - 36753522
AN - SCOPUS:85147783287
SN - 1935-2727
VL - 17
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 2
M1 - e0011067
ER -