PROTECTIVE HUMORAL RESPONSE AGAINST PNEUMOCOCCAL INFECTION IN MICE ELICITED BY RECOMBINANT BACILLE CALMETTE-GUERIN VACCINES EXPRESSING PNEUMOCOCCAL SURFACE PROTEIN-A

Pneumococcal surface protein A (PspA), a cell-surface protein present on all strains of pneumococci, has been shown to elicit protective ant ibody responses in mice in the absence of capsular polysaccharide. Whe reas PspA is polymorphic, considerable cross-reactivity and cross-prot ection have been demonstrated among PspA proteins of pneumococci exhib iting different capsular and PspA serotypes. A gene segment encoding t he nonrepetitive variable NH2-terminal portion of PspA has been cloned into three distinct recombinant Bacille Calmette-Guerin (rBCG) vector s, allowing for expression of PspA as a cytoplasmic or secreted protei n, or a chimeric exported membrane-associated lipoprotein. All rBCG-Ps pA strains elicited comparable anti-PspA ELISA titers, ranging from 10 (4) to 10(5) (reciprocal titers) in both BALB/c and C3H/HeJ mice. Howe ver, protective responses were observed only in animals immunized with the rBCG-PspA vaccines expressing PspA as a secreted protein or chime ric exported lipoprotein. In addition, anti-PspA immune sera elicited by the rBCG vaccines passively protected X-linked immunodeficient mice from lethal challenge with the highly virulent, encapsulated WU2 stra in of Streptococcus pneumoniae and two additional virulent strains exh ibiting heterologous PspA and capsular serotypes. These studies confir m previous PspA immunization studies showing cross-protection against heterologous serotypes of S. pneumoniae and demonstrate a potential fo r rBCG-based PspA vaccines to elicit protective humoral responses agai nst pneumococcal disease in humans.