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Biochemical and molecular genetic characterization of novel protective antigens against group B Streptococcus


This application proposes a postdoctoral training period in genomic approaches to development of vaccines against bacterial pathogens. Until recently, vaccine research followed a series of bottom up steps beginning from identification of virulence factors through serological or genetic approaches. With the availability of complete genome sequence of bacterial pathogens, this process has been reversed.

From the genome sequence, every protein produced by the bacteria can be identified. High throughput cloning and expression of the predicited proteins leads to the production of several hundred recombinant antigens which can be tested in appropriate models of immunogenicity. This approach has been taken at the host institute to identify several novel candidates for a vaccine against Group B Streptococcus (GBS). In collaboration with TIGR, the sequence of the genome of a serotype V strain of GBS was determined. Using the "Reverse Vaccinology" approach several novel protective antigens against GBS have been identified.

A key protective antigen, antigen 80, identified in the genomic screen, is a surface exposed protein containing the LPXTG motif involved in cell wall attachment and shares some similarity with proteins involved in extracellular matrix adhesion. The overall objective of this proposal is to characterize structure, function and regulation of expression of antigen 80 to better understand its role in GBS physiology and/or pathophysiology.

Biochemical, molecular genetic and bioinformatic approaches will be taken to identify structural characteristics of the protein, to identify functional domains within the protein and to define protective epitopes exposed on the surface of the bacteria. Proteomic and microarray technology will be used to study the regulation of expression of the antigen during experimental infection in mice. We expect the results to contribute to our understanding of GBS pathogenesis.

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