Natural antibodies in normal human sera inhibit Staphylococcus aureus capsular polysaccharide vaccine efficacy.

Publication Type:

Journal Article


Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2012)


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 S. 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 if natural antibody to PNAG in normal human sera (NHS) had a similar deleterious effect.Methods. Evaluations of 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 sera of healthy subjects with natural antibody to PNAG to which immunization-induced animal antibodies to CP antigens were added.Results. Antibodies to PNAG and CP that mutually interfered with opsonic killing of S. aureus were detected in 9/15 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.