Previous work in our laboratory has led to the identification of a pneumococcal surface protein (PspA) which is a virulence factor for pneumococci and also elicits antibodies which can protect mice in a pneumococcal bacteremia model. Immunization of mice with purified PspA, and N-terminal fragments of PspA, can protect against otherwise fatal pneumococcal infection. Protective monoclonal antibodies (MAbs) recognize epitopes in the N-terminaI half of PspA. This portion of the protein is responsible for the serologic diversity seen among PspAs from various pneumococcal strains. Recent data from our laboratory shows that, in addition to pspA, nearly all pneumococcal strains contain a second sequence in their genomes which hybridizes with a cloned pspA DNA probe. Using cloned fragments of pspA our laboratory has determined that the 3' end of pspA is highly homologous with this second,pspA-like sequence. The pspA-Iike sequence shows less homology with the 5' region of pspA and probes from this region do not consistently detect, under conditions of high stringency hybridization, the pspA-like sequence in every strain. I propose to examine this second sequence to determine if it encodes a pneumococcal surface protein similar to PspA, and also determine if the putative protein is able to elicit a protective immune response. I will also investigate whether this second locus provides a mechanism for genetic recombination with pspA, enabling pneumococci to modulate the antigenic epitopes within PspA.
