The Human Antibody Response to Streptococcal C5a Peptidase

Abstract

An ELISA was developed to measure antibody, both IgG and IgA, against the streptococcal C5a peptidase (SCP), in human sera and saliva. Generally, sera and saliva from young, uninfected children lacked antibody to SCP. In contrast, most sera and saliva specimens from healthy adults had measurable levels of anti-SCP IgG and SCP-specific secretory IgA (anti-SCP sIgA). Paired acute and convalescent sera from patients with streptococcal pharyngitis possessed significantly higher levels of anti-SCP IgG than did sera from healthy individuals. Sera containing high concentrations of anti-SCP immunoglobulin were capable of neutralizing SCP activity. A survey of healthy adults and children also showed that the latter were significantly less likely to have anti-SCP sIgA in their saliva. Detection of this antibody in greater than 90% of the saliva specimens obtained from children who had recently experienced streptococcal pharyngitis demonstrated that children can produce a secretory response. This is thought to be the first report of a secretory IgA response in humans to a somatic antigen of Streptococcus pyogenes.

Pathogenesis of Group A Streptococcal Infections

“…Moreover, intranasal immunization of mice produced a vigorous serum and secretory antibody response that enhanced clearance of the bacteria from the oral mucosa of mice (264). Although fewer than 15% of children under 10 years of age exhibit measurable antibody against C5a peptidase, most adults have evidence of a strong immune response to this streptococcal protein (396). These findings prompted investigators to suggest that the immune response to the C5a peptidase may account for the relative resistance of adults to infection.…”

Surface Proteins ofStreptococcus agalactiaeand Related Proteins in Other Bacterial Pathogens

“…Immunization of mice with recombinant ScpB, which is almost identical to ScpA, also reduced the ability of S. pyogenes to colonize mouse tissues (43). Of note, ScpA is immunogenic in humans, as shown by the appearance of anti-ScpA antibodies during many (but not all) natural S. pyogenes infections (185,228). However, anti-ScpA antibodies do not appear to be opsonic (228), possibly because the S. pyogenes strains also express the antiphagocytic M protein, but they might protect against infection by inhibiting adhesion to (or invasion of) epithelial cells.…”

Active and Passive Intranasal Immunizations with Streptococcal Surface Protein C5a Peptidase Prevent Infection of Murine Nasal Mucosa-Associated Lymphoid Tissue, a Functional Homologue of Human Tonsils

“…Antibody directed at the peptidase could act at three levels: it could neutralize protease activity, block uptake of streptococci by M cells or epithelial cells (32), and/or opsonize the bacteria. Consistent with these possibilities are the facts that human sera containing high titers of anti-SCPA IgG are able to inhibit C5ase activity (28), anti-SCPA antibodies can reduce invasion of A549 cells (32), and anti-SCPB can promote phagocytosis of group B streptococci in vitro (7). No antipeptidase antibody has been shown to opsonize GAS, nor has a correlation between anti-SCPA antibodies and resistance to streptococcal disease in humans been made.…”

“…Immunogenicity of SCPA protein in humans has been reported. O'Connor et al discovered that most healthy adults have measurable levels of anti-SCPA IgG and IgA in their sera and saliva, respectively, whereas these antibodies were considerably less commonly found in these body fluids from children (28). Anti-SCPA IgG concentrations were found to be significantly higher in convalescent-phase than in acute-phase sera from children recently infected with streptococcal pharyngitis, indicating that SCPA is expressed during infection and is highly immunogenic in humans (35).…”

“…Studies from our laboratory have demonstrated that more than 70% of adults have measurable secretory immunoglobulin A (IgA) in their saliva, directed at the surface-bound C5a peptidase (SCPA) (28). In contrast, only 1 in 10 children under the age of 10 years were observed to have anti-SCPA antibodies in their saliva.…”