SORDELLI Daniel Oscar
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 LPN; BUZZOLA FR; ALVAREZ LP; LEE JC; SORDELLI DO
INFECTION AND IMMUNITY
Lugar: Washington DC, USA; Año: 2008 vol. 76 p. 5738 - 5744
The pathogenesis of Staphylococcus aureus infections is influenced by multiple virulence factors that are expressed under variable conditions, and this has complicated the design of an effective vaccine. Clinical trials that targeted the capsule or clumping factor A (ClfA) failed to protect the recipients against staphylococcal infections. We passively immunized lactating mice with rabbit antibodies to the S. aureus capsular polysaccharides serotypes 5 (CP5) or 8 (CP8) or with monoclonal antibodies to clumping factor A (ClfA). Mice administered antibodies to CP5 (or CP8) or ClfA showed significantly reduced tissue bacterial burdens 4 days after intramammary challenge with encapsulated S. aureus strains. After several passages within mice passively immunized with CP-specific antiserum, increasing numbers of stable unencapsulated variants of S. aureus were cultured from the infected mammary glands. These unencapsulated S. aureus variants were internalized in vitro within MAC-T bovine cells in greater numbers compared to their respective encapsulated parental strains. Furthermore, small colony variants (SCVs) were recovered from the infected mammary glands after several passages within mice passively immunized with CP-specific antiserum. The combination of antibodies effectively sterilized mammary glands in a significant number of passively immunized mice. More importantly, passive immunization with antibodies to both CP and ClfA fully inhibited the emergence of unencapsulated escape mutants and significantly reduced the appearance of SCVs. A vaccine formulation comprising CP-conjugates plus a surface-associated protein adhesin may be more effective than either antigen alone in the prevention of S. aureus infections.