Analysis of putative vaccine antigens from streptococcus pneumoniae

Research archive

Streptococcus pneumoniae is a major cause of meningitis, particularly among children and the elderly. With the spread of multiple antibiotic resistance, infections caused by this organism are becoming progressively more difficult to treat. Currently available vaccines, comprising polyvalent pneumococcal polysaccharide and, protein-polysaccharide conjugates, suffer from a number of major limitations. There is therefore a pressing need for new prophylactic and therapeutic measures, and accordingly there has been increasing interest in the development of new vaccines using protein antigens common to all pneumococcal types.

The success of a pathogen in the host requires adaptive responses on the part of the bacteria, with the acquisition of iron one of the most important. Accordingly, given the significance of iron to pathogens and their virulence, bacterial proteins involved in iron uptake appear particularly promising as vaccine antigens. In previous work funded by Meningitis Research Foundation, I have identified a number of novel iron-regulated genes in S. pneumoniae. Analysis of sequence data has identified those likely to be surface exposed, and the complete ORFs have been cloned. The purpose of this proposal is to take this work further: The genes will be expressed, and protein purified, allowing antibody production. The degree of conservation of the antigens will be determined by sequence analysis of a representative population of strains. Collaboration with CAMR will permit murine immunogenicity studies, and clinical evaluation using their bank of human acute and convalescent sera. The ultimate aim of this work is to use a number of these antigens to develop a better, protein-based vaccine.

Results from this study have been published in a scientific journal as follows: