The Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. An important strategy for the prevention of this infection is the immunization of non-immune women. While significant advances have been made toward understanding the role of the capsular polysaccharide in virulence and immunity of GBS, polysaccharide vaccines do not by themselves evoke protective levels of antibodies in all recipients. C proteins are another class of GBS antigen which are capable of eliciting protective immunity and would serve as an ideal candidate for a vaccine, either alone or conjugated to the bacterial capsular polysaccharide. However, these antigens have not been isolated or purified and little is known of their number, structure or function. Preliminary work in our laboratory has led to the partial purification of C proteins and the development of E. coli clones which express C proteins. The major research goal of this proposal is to isolate, purify and characterize, both biochemically and immunologically, the C protein antigens of the type Ia/c (Ic) GBS. The further research goal of this project is to express these protective proteins at high levels in a recombinant system and immunopurify them, in preparation for development of a vaccine. The physician Scientist Award also has the important training goal of preparing the applicant, a clinically trained infectious disease physician, for an independent research career in the field of bacterial pathogenesis. The Award will provide a solid background in basic scientific research principles and methods. Phase I of the Award will stress the broad training of the applicant in research methods in the areas of immunology, biochemistry, microbiology and molecular genetics. This will be accomplished through didactic training as well as through bench research on the isolation of specific C protein antigens of GBS, the development of monoclonal antibodies directed at these antigens and the analysis of cloned DNA sequences which encode C protein expression. This training will be utilized in Phase II to accomplish the important research goal of overexpressing these proteins in recombinant DNA systems.
| Hervas, J A; Gonzalez, L; Gil, J et al. (1993) Neonatal group B streptococcal infection in Mallorca, Spain. Clin Infect Dis 16:714-8 |
| Madoff, L C; Michel, J L; Gong, E W et al. (1992) Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein. Infect Immun 60:4989-94 |
