Because of the potential bioterrorism threat, the development of a safe and effective B. pseudomallei vaccine is a national and worldwide goal. The Applied Proteomics Laboratory at UC Irvine has developed a high throughput protein expression system called PCR Express which can be used to rapidly generate complete proteomes from any sequenced microorganism, including the Class A, B & C Bioterrorism Agents. The technology allows hundreds of different genes to be expressed directly from their PCR products at the rate of hundreds of different proteins per week. Here the Burkholderia pseudomallei proteome will be generated and applied to the problem of identifying antigens recognized by B-cells and T-cells that will be useful in a subunit vaccine against the agent. The first form of the proteome will be on microarray chips which will be used to quantify serum antibody titers from BALB/c mice vaccinated with a rationally attenuated auxotroph of B. pseudomallei (2D2) and humans naturally exposed to B. pseudomallei in endemic regions of NE Thailand against each of the individual bacterial proteins. For the second proteome format, each individual protein will be purified and presented in a form that will enable them to be used in T cell restimulation assays in vitro using either spleen cells from 2D2 vaccinated mice or whole blood from exposed human populations. T cell activation will be determined by ELISA assay for secretion of lFN?. The responsive antigens identified by this Vaccine Antigen Scan will be tested for their efficacy in a murine model of infection with B. pseudomallei and, because of the extensive genetic similarity between B. pseudomallei and B. mallei, in animal models of glanders. This quantitative humoral and cellular immune response scan will produce the first complete profile of the immune response against B. pseudomallei in humans and experimental animals and will identify the most effective candidate antigens for development of a DNA or subunit vaccine against human melioidosis and glanders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI061363-04
Application #
7286108
Study Section
Special Emphasis Panel (ZAI1-LR-M (M1))
Program Officer
Mukhopadhyay, Suman
Project Start
2004-09-01
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$996,535
Indirect Cost
Name
University of California Irvine
Department
Miscellaneous
Type
Organized Research Units
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Jing, Lichen; Schiffer, Joshua T; Chong, Tiana M et al. (2013) CD4 T-cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence. J Virol 87:2617-27
Varga, John J; Vigil, Adam; DeShazer, David et al. (2012) Distinct human antibody response to the biological warfare agent Burkholderia mallei. Virulence 3:510-4
Conejero, Laura; Patel, Natasha; de Reynal, Melanie et al. (2011) Low-dose exposure of C57BL/6 mice to burkholderia pseudomallei mimics chronic human melioidosis. Am J Pathol 179:270-80
Chu, Karen K; Tippayawat, Patcharaporn; Walker, Nicola J et al. (2011) CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis. Eur J Immunol 41:107-15
Easton, Anna; Haque, Ashraful; Chu, Karen et al. (2011) Combining vaccination and postexposure CpG therapy provides optimal protection against lethal sepsis in a biodefense model of human melioidosis. J Infect Dis 204:636-44
Tippayawat, Patcharaporn; Pinsiri, Maneerat; Rinchai, Darawan et al. (2011) Burkholderia pseudomallei proteins presented by monocyte-derived dendritic cells stimulate human memory T cells in vitro. Infect Immun 79:305-13
Suwannasaen, Duangchan; Mahawantung, Jirawan; Chaowagul, Wipada et al. (2011) Human immune responses to Burkholderia pseudomallei characterized by protein microarray analysis. J Infect Dis 203:1002-11
Magnan, Christophe N; Zeller, Michael; Kayala, Matthew A et al. (2010) High-throughput prediction of protein antigenicity using protein microarray data. Bioinformatics 26:2936-43
Yang, Zheng Rong; Lertmemongkolchai, Ganjana; Tan, Gladys et al. (2009) A genetic programming approach for Burkholderia pseudomallei diagnostic pattern discovery. Bioinformatics 25:2256-62
Pankla, Rungnapa; Buddhisa, Surachat; Berry, Matthew et al. (2009) Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis. Genome Biol 10:R127

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