Antibodies to capsular polysaccharide and clumping factor A prevent mastitis and the emergence of unencapsulated and small colony variants of Staphylococcus aureus in mice

TUCHSCHERR L; BUZZOLA F; ALVAREZ L; LEE J; SORDELLI D

INFECTION AND IMMUNITY

ASM Press

Año: 2008 vol. 76 p. 5738 - 5744

0019-9567

The pathogenesis of Staphylococcus aureus infections is influenced by multiple virulence factors that areexpressed under variable conditions, and this has complicated the design of an effective vaccine. Clinical trialsthat targeted the capsule or clumping factor A (ClfA) failed to protect the recipients against staphylococcalinfections. We passively immunized lactating mice with rabbit antibodies to S. aureus capsular polysaccharide(CP) serotype 5 (CP5) or CP8 or with monoclonal antibodies to ClfA. Mice immunized with antibodies to CP5or CP8 or with ClfA had significantly reduced tissue bacterial burdens 4 days after intramammary challengewith encapsulated S. aureus strains. After several passages in mice passively immunized with CP-specificantiserum, increasing numbers of stable unencapsulated variants of S. aureus were cultured from the infectedmammary glands. Greater numbers of these unencapsulated S. aureus variants than of the correspondingencapsulated parental strains were internalized in vitro in MAC-T bovine cells. Furthermore, small-colonyvariants (SCVs) were recovered from the infected mammary glands after several passages in mice passivelyimmunized with CP-specific antiserum. A combination of antibodies effectively sterilized mammary glands ina significant number of passively immunized mice. More importantly, passive immunization with antibodies toboth CP and ClfA fully inhibited the emergence of unencapsulated “escape mutants” and significantly reducedthe appearance of SCVs. A vaccine formulation comprising CP conjugates plus a surface-associated proteinadhesin may be more effective than either antigen alone for prevention of S. aureus infections.