Protective efficacy of antibodies to the Staphylococcus aureus type 5 capsular polysaccharide in a modified model of endocarditis in rats.
The protective efficacy of antibodies to the Staphylococcus aureus type 5 capsular polysaccharide (CP5) was examined in a modified model of catheter-induced endocarditis. Rats were catheterized by surgically passing a polyethylene catheter through the right carotid artery and aortic valve into the left ventricle. The following day, the rats were injected by the intraperitoneal (i.p.) route with immunoglobulin G (IgG) purified from nonimmunized rabbits or from rabbits immunized with a conjugate vaccine composed of CP5 and CP8 linked covalently to recombinant Pseudomonas aeruginosa exotoxoid A. One day after passive immunization, the animals were challenged i.p. with one of three serotype 5 S. aureus isolates (strain Reynolds, Lowenstein, or VP) or nontypeable strain 521. Protection was evaluated by comparing quantitative cultures of blood, endocardial vegetations, and kidneys from control and immune animals. For experiments performed with S. aureus Reynolds and Lowenstein, rats given capsular antibodies (645 microg of CP5-specific IgG) showed a significantly (P < 0.05) lower prevalence of endocarditis than rats injected with nonimmune IgG. Similarly, quantitative cultures of the blood, kidneys, and aortic valve vegetations revealed that fewer S. aureus cells were recovered from rats given capsule-specific IgG than from rats administered nonimmune IgG. Rats challenged with strain VP were protected with 1.145 mg of CP5-specific IgG. Capsular antibodies did not protect against infection elicited by a nontypeable strain. These results demonstrate that capsular antibodies elicited by immunization with a polysaccharide-protein conjugate vaccine protect experimental animals against serotype 5 S. aureus infection in a modified model of endocarditis.
Lee
J C
JC
Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. jean.lee@channing.harvard.edu
Park
J S
JS
Shepherd
S E
SE
Carey
V
V
Fattom
A
A
D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use*; D016667:Bacterial Capsules / Q000276:immunology*; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000517:prevention & control*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009895:Opsonin Proteins; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000145:classification / Q000276:immunology
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D009895:Opsonin Proteins; C054106:capsular polysaccharide, type 5, Staphylococcus aureus