Effect of O acetylation of Neisseria meningitidis serogroup A capsular polysaccharide on development of functional immune responses.
The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis serogroup A polysaccharide (PS) was examined in studies using human sera and mouse immunization. In 17 of 18 postimmunization human sera, inhibition enzyme-linked immunosorbent assay indicated that the majority of antibodies binding to serogroup A PS were specific for epitopes involving O-acetyl groups. Studies with mice also showed an essential role for O-acetyl groups, where serum bactericidal titers following immunization with de-O-acetylated (de-O-Ac) conjugate vaccine were at least 32-fold lower than those following immunization with O-Ac PS-conjugate vaccine and 4-fold lower than those following immunization with native capsular PS. Inhibition studies using native and de-O-Ac PS confirmed the specificity of murine antibodies to native PS. The dramatic reduction in immunogenicity associated with removal of O-acetyl groups indicates that O acetylation is essential to the immunogenic epitopes of serogroup A PS. Since levels of bactericidal antibodies are correlated with protection against disease, O-acetyl groups appear to be important in protection.
Berry
David S
DS
Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892, USA.
Lynn
Freyja
F
Lee
Che-Hung
CH
Frasch
Carl E
CE
Bash
Margaret C
MC
D000107:Acetylation; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D016667:Bacterial Capsules / Q000276:immunology*; D005260:Female; D006801:Humans; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D019081:O Antigens / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology
D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D019081:O Antigens; D018074:Vaccines, Conjugate