Just one day before the NIH announced its roadmap (see story, p. 1), the National Institute of Allergy and Infectious Diseases released a progress report on biodefense that detailed 50 current biodefense initiatives — including several in the area of proteomics that it described as directly addressing earlier recommendations made by a Blue Ribbon Panel.
In response to a recommendation to “develop rapid, inexpensive, and broad-based clinical diagnostics approaches using genomics and proteomics,” the report noted that the NIAID had established three initiatives: Biodefense Partnerships; the Cooperative Research for the Development of Vaccines, Adjuvants, Therapeutics, Immunotherapeutics, and Diagnostics for Biodefense Program; and Identifying Targets for Therapeutic Interventions Using Proteomic Technologies. The report said that the NIAID had so far received 75 applications for grants applying genomics and proteomics to address the first two initiatives and that awards would be made before the end of financial year 2003. For the third grant, awards were planned for FY2004.
In response to a recommendation to “encourage structural genomics and proteomics for the targeted development of drugs, vaccines, and diagnostics,” the NIAID noted that it was currently funding a Biodefense Proteomics Collaboratory, based at the University of Texas Medical Branch, for using high-throughput proteomics to identify targets from arenaviruses and Lassa virus.
T-Cell Array Project
One recent broad-based initiative discussed in the report, establishing Cooperative Centers for Translational Research on Human Immunology and Biodefense, last month awarded $85 million to several institutions — including $16 million to the University of Massachusetts Medical School (see GenomeWeb News, 9-19-03) — for the study of the human immune response to bioterror agents. ProteoMonitor spoke with investigators at UMass last week about the large proteomics component to this grant.
Lawrence Stern, a pathology professor at the medical school, said that his group would use mass spec and protein array technology to look at T-cell response to “exotic viruses” — in particular, pox viruses, hantaviruses, and flaviviruses like West Nile. “It’s possible that some of these viruses elicit particular kinds of T-cells or particular features in the T-cells that we’ll be able to see by looking at the properties of the T-cell,” Stern said.
A large part of the grant, according to Stern, will be devoted to identifying the particular epitopes of the virus that are presented to the immune system and recognized. “That’s important in being able to develop ways to track the infection and possibly also for the development of vaccines — so you could prime the immune system and when it saw the pieces that are being recognized, it would be able to combat them,” he said. Stern said that developing a vaccine using a particular protein or peptide made by the virus, rather than using the whole virus, was of interest to scientists hoping to reduce the side effects associated with vaccines such as the one for smallpox.
James Evans, director of the proteomics and mass spectrometry facility at UMass, said that the facility was ordering a Thermo Finnigan LTQ for the mass spec experiments. The LTQ will replace the Waters Q-TOF currently in use as the primary mass spec for the study, due to its “superior sensitivity and scanning speed,” Evans said.
In addition to mass spec analysis, Stern will also use protein arrays of MHC peptide complexes consisting of recombinant proteins loaded with particular candidate peptide antigens to test for T-cell response. MHC proteins are responsible for presenting viral peptides on the cell during an immune response. Candidate peptides would be based on known pathogen genomes, with the initial list being trimmed down “as a result of crystal structures and biochemical work on MHC biology.” Presently the arrays are in the prototype phase, but Stern hopes that by the end of the five-year grant time frame, he will have made progress toward applying the arrays to clinical samples.