RESUMO
The Global Alliance for Genomics and Health (GA4GH) is developing a suite of coordinated standards for genomics for healthcare. The Phenopacket is a new GA4GH standard for sharing disease and phenotype information that characterizes an individual person, linking that individual to detailed phenotypic descriptions, genetic information, diagnoses, and treatments. A detailed example is presented that illustrates how to use the schema to represent the clinical course of a patient with retinoblastoma, including demographic information, the clinical diagnosis, phenotypic features and clinical measurements, an examination of the extirpated tumor, therapies, and the results of genomic analysis. The Phenopacket Schema, together with other GA4GH data and technical standards, will enable data exchange and provide a foundation for the computational analysis of disease and phenotype information to improve our ability to diagnose and conduct research on all types of disorders, including cancer and rare diseases.
RESUMO
F tularensis is among of the most virulent pathogens known, yet it remains poorly understood. Correlates of protection involve robust CD4+ and CD8+ T cell responses, and the production of IFN-gamma, TNF-alpha, and IL-12. Novel approaches may be required to develop a safe vaccine that achieves these correlates. In contrast to other types of vaccines, epitope-based vaccines combine targeted biologic activity with the practical advantages of platform independence, scalable synthesis and manufacturing. These advantages, coupled with the proof of principle achieved with an epitope-based tularemia vaccine, suggest that this approach might be applied more widely to develop vaccines against other pathogens, intracellular bacteria most notably.
Assuntos
Vacinas Bacterianas , Francisella tularensis/efeitos dos fármacos , Interferon gama/biossíntese , Linfócitos T/efeitos dos fármacos , Tularemia/prevenção & controle , Fator de Necrose Tumoral alfa/biossíntese , Animais , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/farmacologia , Vacinas Bacterianas/uso terapêutico , Mapeamento de Epitopos , Francisella tularensis/patogenicidade , Humanos , Imunidade Celular/efeitos dos fármacos , Linfócitos T/imunologia , Tularemia/imunologiaRESUMO
New vaccine candidates that might better control the worldwide prevalence of Mycobacterium tuberculosis (Mtb) have yet to be described. Strong CD4+ T cell-mediated immune response (CMI) is correlated with protection from the development of TB disease; however, the selection of suitable vaccine antigens has been thwarted by the size and complexity of the (Mtb) proteome, and by the relative difficulty of delivering these antigens in the right immunological context. One possible solution is to develop immunotherapeutic vaccines for TB that are based on T cell epitopes representing multiple antigens. This text illustrates the stepwise development of epitope-driven vaccines from in silico epitope mapping to testing the vaccine in a live Mtb challenge model. First, we used the whole genome Mtb microarray to identify bacterial proteins expressed under the conditions thought to model Mtb survival and replication in human macrophages. Eighteen of these proteins were also found by Behr et al. to be absent from at least one strain of BCG; the sequences of these eighteen proteins were then screened for T-cell epitopes using the immuno-informatics algorithm, EpiMatrix. Of the seventeen representative epitopes evaluated in ELISpot assays, all seventeen were confirmed to elicit interferon (IFN)-gamma secretion by PBMC from Mtb-exposed subjects. A parallel live Mtb challenge study in mice showed prototype epitope-based TB vaccines to be robustly immunogenic but not as effective as BCG. These experiments illustrate the use of immuno-informatics tools for vaccine development and describe a pathway for the development of a more effective, epitope-driven, immunotherapeutic vaccine for TB.