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Meeting Report a Roadmap for the Immunomics of Category A–C

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Meeting Report a Roadmap for the Immunomics of Category A–C View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Immunity, Vol. 22, 155–161, February, 2005, Copyright ©2005 by Elsevier Inc. DOI 10.1016/j.immuni.2005.01.009 A Roadmap for the Immunomics Meeting Report of Category A–C Pathogens Alessandro Sette,* Ward Fleri, Bjoern Peters, and reemerging pathogens, including potential bioter- Muthuraman Sathiamurthy, rorism agents. Accordingly, an aggressive program has Huynh-Hoa Bui, and Stephen Wilson been initiated to support the large-scale identification La Jolla Institute for Allergy and Immunology of immune epitopes derived from NIAID category A–C pa- 10355 Science Center Drive thogens (Large-Scale Antibody and T cell Epitope Dis- San Diego, California 92121 covery Program). The same programmatic area has sponsored the creation of a national database, the Im- mune Epitope Database and Analysis Resource (IEDB), to house existing epitope data as well as data resulting The National Institute of Allergy and Infectious Dis- from these novel discovery efforts. It is anticipated that eases (NIAID), part of the National Institutes of Health these data will be made freely available to the scientific (NIH), recently awarded 14 contracts to fund the community. The IEDB will also house a general analysis Large-Scale Antibody and T Cell Epitope Discovery resource, which will host bioinformatics tools devel- Program. This initiative is designed to identify immune oped to assist in epitope prediction and data analysis, epitopes from selected infectious agents utilizing com- and facilitate vaccine development (http://www.niaid. plementary methods for epitope discovery. NIAID will nih.gov/contract/archive/rfp0331.pdf and http://www. make information on each newly identified epitope niaid.nih.gov/contract/archive/RFP0343-0.pdf). A dia- freely available to scientists worldwide through the gram illustrating the major components of the IEDB and Immune Epitope Database and Analysis Resource the Large-Scale Antibody and T cell Epitope Discovery (IEDB), currently under development. On October 12– Program is shown in Figure 1. 14, 2004, representatives of NIAID met in San Diego, The rationale for establishing both initiatives stems California, with a group of investigators from various from the realization that one of the main impediments research institutions to discuss progress and plans to accurate and rapid development of vaccines and di- for the large-scale epitope discovery projects and for agnostics for Category A–C pathogens is the scarcity the establishment of the IEDB. It is anticipated that of basic information relating to the epitopes recognized these initiatives will establish detailed maps of im- by adaptive immune responses. Indeed, very little infor- mune reactions toward several important complex pa- mation exists relating to the molecular details of im- thogens, which in turn will foster development of new mune responses to most of these pathogens. This pau- diagnostic, immune-based therapeutic, and vaccine city of information hampers the monitoring of immune programs. Herein is an account of the meeting and responses themselves either in the course of natural its results. infection or in response to experimental vaccines. This lack of knowledge also hinders basic investigations fo- Introduction cused on pathogen/host interactions, studies to deter- Recent times have seen an explosion of knowledge re- mine potential immune evasion or escape mechanisms lated to the genetic and protein structures of microbes of a given pathogen, and the correlation of vaccination and complex organisms alike. This genomics and pro- with protective immunity. teomics era is now followed by the development of Representatives from NIAID met with investigators more-specialized collections of data relating to particu- involved in the creation of the IEDB and those recipi- lar aspects of cell biology and immunology. In this ents of contracts through the Large-Scale Antibody and context, the immunome can be defined as the detailed T cell Epitope Discovery Program on October 12–14, map of immune reactions of a given host interacting 2004, in San Diego, CA. The three-day meeting began with a foreign antigen, and immunomics can be defined with a presentation detailing the creation of the IEDB, as the study of immunomes. its objectives, and its planned functionality at launch in In the aftermath of the 9/11 attacks, federal support 2005. This initial presentation was followed by a series of research in the area of biodefense has dramatically of presentations from representatives of the various in- increased. A key element of the National Institute of stitutions who had been awarded contracts to work on Allergy and Infectious Diseases (NIAID), part of the Na- epitope identification and collaborate in populating tional Institutes of Health (NIH), Biodefense Research the IEDB. program to address the potential threat posed by cate- gory A–C pathogens (as listed at http://www2.niaid.nih. The Immune Epitope Database gov/biodefense/bandc_priority.htm) is the generation Started in December 2003, the IEDB will be the world’s and gathering of accurate scientific information related largest database specifically devoted to immune epi- to these dangerous agents. It is anticipated that these tope data and is expected to facilitate explorations of data will in turn lead to the generation of new research immunity to infectious agents as well as immune-medi- tools and to the discovery and development of new di- ated disorders. The database will allow researchers agnostics, vaccines, and therapeutics, for emerging around the globe to quickly access key information on immune responses and to share and analyze data in an unprecedented manner. It is expected to be publicly *Correspondence: [email protected] available in late 2005 and will include antibody and T Immunity 156 Figure 1. Integration of Various Components of the Large-Scale Antibody and T cell Epi- tope Discovery Program and IEDB The IEDB will include data that is collected from existing databases, curation from the literature and patent sources by IEDB staff, and direct submissions to the database. Among the most important and substantial submission data sets will be those from each of the Large-Scale Antibody and T cell Epi- tope Discovery Program research teams (see Table 1 for more detail). Once submitted and further annotated, the data can be re- trieved by users at large over the Internet using a standard web browser. The results of their queries can be exported and/or further analyzed online utilizing tools provided in the analysis resources that are directly hosted at or linked to the IEDB. cell epitopes from infectious pathogens, as well as ex- topes. MHC binding does not guarantee, per se, that perimental and self-antigens. A key element in the the resulting complex will engage specific TCRs and nation’s battle against infectious diseases, and in line thereby meet the definition of an epitope. However, the with federal research goals, the database will place IEDB will also include data relating to MHC binding and particular emphasis on NIAID Category A–C pathogens, natural MHC ligands because compounds capable of such as anthrax, smallpox, West Nile virus, influenza, binding MHC molecules have the potential of being im- and SARS. Detailed information from humans, nonhu- munogenic or antigenic for T cells. man primates, rodents, and any species for which de- The logical design of the database and how epitope tailed immune response information is available will be data will be represented were discussed by Alessandro included. In terms of scale, the IEDB structure will allow Sette and Stephen Wilson (LIAI, San Diego, CA). Intrin- the inclusion of a large number of records (several hun- sic epitope features included in the IEDB are the molec- dred thousand) and accommodate further growth (e.g., ular structure of the epitope, binding affinity for dif- from the large-scale epitope discovery programs). ferent MHC receptors or antibody molecules, affinity of Extensive annotation will allow context representation MHC/epitope complexes for antibodies and TCRs of coupled with extensive use of flexible query strategies, defined sequence, and the phylogenetic origin and which will allow users to customize searches to the de- conservation of the epitope structure in related organ- sired level of stringency and to include or to exclude isms. Available 3-D structures of antibody epitopes, an- various types of information, as described in more de- tibody/epitope complexes, epitope/MHC, and epitope/ tail below. At the conference, the progress to date on MHC/TCR complexes will also be included. These fea- the design of the database was presented. Research- tures are unequivocally specified with relative ease. ers from the La Jolla Institute for Allergy and Immunol- Most importantly, they are singularly associated with a ogy (LIAI), which is in charge of its development, sought given epitope structure or epitope/receptor combina- feedback from attendees to ensure that the database tion. Other features, such as antigenicity and immuno- will be responsive to the needs of the scientific com- genicity, are not intrinsically associated with a given munity. epitope or structure but rather are highly context de- pendent. To meaningfully specify antigenicity or immu- Progress in the Development of the IEDB nogenicity, information regarding the structure of the Perhaps the two most crucial issues in the design of epitope
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