Staphylococcus aureuscapsule type 8 antibodies provide inconsistent efficacy in murine Models of staphylococcal infection

Abstract

Staphylococcus aureus is a clinically important capsule-forming bacterium. The capsule polysaccharide (CPs) occurs as different chemical structures depending on the serotype of the organism, but one form, capsular polysaccharide type 8 (CPs8) found in clinical isolates, is largely unstudied. The potential of CPs8 as a vaccine target was evaluated using two approaches. The first approach used a conjugate vaccine, made by chemically linking purified CPs8 to the outer membrane protein complex of N. meningitidis serotype B (OMPC). In efficacy studies, the CPs8-OMPC conjugate vaccine was immunogenic in Balb/c mice, however the immune response gave no protection from death after a lethal intravenous (IV) challenge with S. aureus Becker. In the second approach, two monoclonal antibodies were produced against CPs8 (mAbs 8E8 and 1C10). These were found to have functional activity in an opsonophagocytic killing assay (OPA), and provided protection from a lethal challenge when bacteria were pre-opsonized ex vivo before intra-peritoneal (IP) challenge. However, mAb 8E8 was not efficacious in the lethal challenge model, in which antibodies were passively transferred to the peritoneum and the animals were infected via the tail vein 18-24 h later. Additionally, the monoclonal antibodies did not opsonize capsule-expressing S. aureus Becker obtained from in vivo growth conditions. These results indicated that functional capsule antibodies may not be sufficient for protection from S. aureus under all in vivo conditions.

Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

“…17 However, when mice passively immunized with CP8-specific mAb 5A6 were challenged with three other S. aureus isolates (MN8, ST80-16, or Wright), no protection against bacteremia was observed. This finding is consistent with a report by Cook et al 33 in which 800 mg of a CP8 mAb or goat anti-CP8 IgG delivered by the intraperitoneal (IP) route did not protect mice against a lethal intravenous dose of S. aureus MCL8538 (a CP8C MLST15 skin isolate). Similarly, our data showing that polyclonal CP8 antiserum significantly reduced Reynolds (CP8) bacteremia but not bacteremia provoked by strain ST80-16 suggest that the lack of protective efficacy against clinical S. aureus isolates is not limited to CP8 mAbs.…”

“…Because there is a paucity of evidence supporting the protective efficacy of CP8 antibodies, 33 we examined whether CP8 mAb 5A6 would reduce bacteremia provoked by additional serotype 8 isolates. Compared to mice given isotype control mAbs, mice passively immunized with 100 mg CP8 mAb 5A6 and challenged 24 h later with serotype 8 S. aureus strains ST80-16, MN8, or Wright showed no significant differences in bacteremia levels (Fig.…”

Selection and Characterization of Murine Monoclonal Antibodies toStaphylococcus aureusIron-Regulated Surface Determinant B with Functional Activity In Vitro and In Vivo

“…The OPK assay was described previously (5). OPK activity was defined as a Ն50% reduction of the numbers of CFU in the test MAb reaction mixtures compared to the numbers of CFU in reaction mixtures with an isotype MAb control.…”

“…Prepared glycerol stocks of S. aureus passaged two to three times under iron-starved conditions (in RPMI medium) were used to evaluate MAbs for IsdB binding, as previously described (5,15).…”

Memory AND effector cells in children with bacterial infections of the gastrointestinal and respiratory tracts

“…In addition, because they produce large amounts of secretory IgA, B lymphocytes play an important role in intestinal mucosal immunity [18]. In patients infected with encapsulated bacteria, such as Haemophilus influenzae and Streptococcus pneumoniae, it has been observed that the absolute numbers of peripheral B lymphocytes are increased; the bacterial capsule is a potent immunogenic component that stimulates the synthesis of IgM and other Ig isotypes in B lymphocytes [19].…”