Prophylactic and therapeutic efficacy of antibodies to a capsular polysaccharide shared among vancomycin-sensitive and -resistant enterococci.
Enterococci are important nosocomial pathogens that are increasingly difficult to treat due to intrinsic and acquired resistance to antibiotics, including vancomycin. A recently described capsular polysaccharide (CP) isolated from Enterococcus faecalis 12030 was used to evaluate the potential efficacy of active or passive immunotherapy regimens as adjunctive treatments. Evaluation of protective efficacy was carried out in immunocompetent mice challenged intravenously (i.v.) with live enterococci. In nonimmune mice, i.v. inoculations resulted in high levels of bacteria in kidneys, spleens, and livers 5 days after challenge. Mice immunized with four 10-microg doses of CP antigen/mouse were protected against challenge with the homologous E. faecalis strain. High-titer opsonic immunoglobulin G was also induced by immunizing rabbits with the purified CP, and passive transfer of this antiserum to mice produced significantly lower bacterial counts in organs than did normal rabbit serum or sterile saline. Antibodies to the polysaccharide isolated from E. faecalis 12030 were protective against Enterococcus faecalis OG1RF and against two serologically related, vancomycin-resistant Enterococcus faecium clinical isolates. Antibodies to this CP antigen were also effective as a therapeutic reagent in mice when passive therapy was initiated 48 h after live bacterial challenge. These data indicate that CP antigens from enterococci are potential targets of protective antibodies and that these antibodies may be useful for prophylaxis and treatment of enterococcal infections.
Huebner
J
J
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. jhuebner@channing.harvard.edu
Quaas
A
A
Krueger
W A
WA
Goldmann
D A
DA
Pier
G B
GB
D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use*; D016667:Bacterial Capsules / Q000737:chemistry / Q000276:immunology*; D013293:Enterococcus faecalis / Q000276:immunology*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000517:prevention & control*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D009895:Opsonin Proteins / Q000276:immunology; D013154:Spleen / Q000382:microbiology; D013682:Teichoic Acids / Q000032:analysis; D014611:Vaccination; D020713:Vancomycin Resistance / Q000276:immunology*
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D013682:Teichoic Acids