Natural antibodies in normal human serum inhibit Staphylococcus aureus capsular polysaccharide vaccine efficacy.
BACKGROUND
Vaccines against Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae type b induce functional opsonic or bactericidal antibodies to surface capsular polysaccharides (CP). Targeting the comparable Staphylococcus aureus CP seems logical, but to date such efforts have failed in human trials. Studies using immunization-induced animal antibodies have documented interference in opsonic and protective activities of antibodies to CP by antibodies to another S. aureus cell surface polysaccharide, poly-N-acetyl glucosamine (PNAG). Here we evaluated whether natural antibody to PNAG in normal human serum (NHS) had a similar deleterious effect.


METHODS
Functional and/or protective activities of antibody to S. aureus CP and PNAG antigens in patients with bacteremia, in mice immunized with combinations of CP and PNAG conjugate vaccines, and in serum samples of healthy subjects with natural antibody to PNAG, to which immunization-induced animal antibodies to CP antigens were added, were evaluated.


RESULTS
Antibodies to PNAG and CP that mutually interfered with opsonic killing of S. aureus were detected in 9 of 15 bacteremic patients. Active immunization of mice with combinations of PNAG and CP conjugate antigens always induced antibodies that interfered with each other's functional activity. Non-opsonic natural antibodies to PNAG found in NHS interfered with the functional and protective activities of immunization-induced antibody to CP antigens during experimental infection with S. aureus.


CONCLUSIONS
Both immunization-induced animal antibodies and natural antibodies to PNAG in NHS interfere with the protective activities of immunization-induced antibody to S. aureus CP5 and CP8 antigens, representing potential barriers to successful use of CP-specific vaccines.
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
David
D
Skurnik
Andrea
A
Kropec
Damien
D
Roux
Christian
C
Theilacker
Johannes
J
Huebner
Gerald B
GB
Pier
D000117:Acetylglucosamine / Q000276:immunology*; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D057134:Antibodies, Neutralizing / Q000097:blood*; D016667:Bacterial Capsules / Q000276:immunology*; D006805:Human Experimentation; D006801:Humans; D051379:Mice; D013203:Staphylococcal Infections / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*
D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D013209:Staphylococcal Vaccines; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine