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Title: A Burkholderia pseudomallei protein microarray reveals serodiagnostic and cross-reactive antigens
Authors: Philip L. Felgner
Matthew A. Kayala
Adam Vigil
Chad Burk
Rie Nakajima-Sasaki
Jozelyn Pablo
Douglas M. Molina
Siddiqua Hirst
Janet S.W. Chew
Dongling Wang
Gladys Tan
Melanie Duffield
Ron Yang
Julien Neel
Narisara Chantratita
Greg Bancroft
Ganjana Lertmemongkolchai
D. Huw Davies
Pierre Baldi
Sharon Peacock
Richard W. Titball
University of California, Irvine
Antigen Discovery Inc.
DSO National Laboratories
Defence Science and Technology Laboratory
University of Exeter
London School of Hygiene & Tropical Medicine
Khon Kaen University
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Multidisciplinary
Issue Date: 11-Aug-2009
Citation: Proceedings of the National Academy of Sciences of the United States of America. Vol.106, No.32 (2009), 13499-13504
Abstract: Understanding the way in which the immune system responds to infection is central to the development of vaccines and many diagnostics. To provide insight into this area, we fabricated a protein microarray containing 1,205 Burkholderia pseudomallei proteins, probed it with 88 melioidosis patient sera, and identified 170 reactive antigens. This subset of antigens was printed on a smaller array and probed with a collection of 747 individual sera derived from 10 patient groups including melioidosis patients from Northeast Thailand and Singapore, patients with different infections, healthy individuals from the USA, and from endemic and nonendemic regions of Thailand. We identified 49 antigens that are significantly more reactive in melioidosis patients than healthy people and patients with other types of bacterial infections. We also identified 59 cross-reactive antigens that are equally reactive among all groups, including healthy controls from the USA. Using these results we were able to devise a test that can classify melioidosis positive and negative individuals with sensitivity and specificity of 95% and 83%, respectively, a significant improvement over currently available diagnostic assays. Half of the reactive antigens contained a predicted signal peptide sequence and were classified as outer membrane, surface structures or secreted molecules, and an additional 20% were associated with pathogenicity, adaptation or chaperones. These results show that microarrays allow a more comprehensive analysis of the immune response on an antigen-specific, patient-specific, and population-specific basis, can identify serodiagnostic antigens, and contribute to a more detailed understanding of immunogenicity to this pathogen.
ISSN: 10916490
Appears in Collections:Scopus 2006-2010

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