Genetic immunization with the region encoding the alpha-helical domain of PspA elicits protective immunity against Streptococcus pneumoniae

Pneumococcal surface protein A (PspA) is a pneumococcal virulence factor ca pable of eliciting protection against pneumococcal infection in mice. Previ ous studies have demonstrated that the protection is antibody mediated. Her e we examined the ability of pspA to elicit a protective immune response fo llowing genetic immunization of mice. Mice were immunized by intramuscular injections with a eukaryotic expression vector encoding the alpha -helical domain of PspA/Rx1. Immunization induced a PspA-specific serum antibody res ponse, and immunized mice survived pneumococcal challenge. Survival and ant ibody responses occurred in a dose-dependent manner, the highest survival r ates being seen with doses of 10 mug or greater. The ability of genetic imm unization to elicit cross-protection was demonstrated by the survival of im munized mice challenged with pneumococcal strains differing in capsule and PspA types. Also, immunized mice were protected from intravenous and intrat racheal challenges with pneumococci. Similar to the results seen with immun ization with PspA, the survival of mice genetically immunized with pspA was antibody mediated. There was no decline in the level of protection 7 month s after immunization. These results support the use of genetic immunization to elicit protective immune responses against extracellular pathogens.