The multivalent pneumococcal
conjugate vaccine is effective against both systemic disease and
otitis media caused by serotypes contained in the
vaccine. However, serotypes not covered by the current
conjugate vaccine may still cause
pneumococcal disease. To address these serotypes and the remaining
otitis media due to Streptococcus pneumoniae, we have been evaluating antigenically conserved
proteins from S. pneumoniae as
vaccine candidates. A previous report identified a 20-kDa
protein with putative human
complement C3-proteolytic activity. By utilizing the publicly released pneumococcal genomic sequences, we found the gene encoding the 20-kDa
protein to be part of a putative open reading frame of approximately 2,400 bp. We recombinantly expressed a 79-kDa fragment (rPhpA-79) that contains a repeated HxxHxH motif and evaluated it for
vaccine potential. The
antibodies elicited by the purified rPhpA-79
protein were cross-reactive to
proteins from multiple strains of S. pneumoniae and were against surface-exposed
epitopes. Immunization with rPhpA-79
protein adjuvanted with
monophosphoryl lipid A (for subcutaneous immunization) or a mutant
cholera toxin,
CT-E29H (for intranasal immunization), protected CBA/N mice against death and
bacteremia, as well as reduced nasopharyngeal colonization, following intranasal challenge with a heterologous pneumococcal strain. In contrast, immunization with the 20-kDa portion of the PhpA
protein did not protect mice. These results suggest that rPhpA-79 is a potential candidate for use as a
vaccine against pneumococcal systemic disease and
otitis media.