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Infection and Immunity, July 2002, p. 3707-3713, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3707-3713.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effect of O Acetylation of Neisseria meningitidis Serogroup A Capsular Polysaccharide on Development of Functional Immune Responses{dagger}

David S. Berry,1,2 Freyja Lynn,1 Che-Hung Lee,1 Carl E. Frasch,1 and Margaret C. Bash1,2*

Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892,1 Department of Pediatric Infectious Diseases, Uniformed Services University of the Health Sciences, Bethesda, Maryland 208142

Received 28 November 2001/ Returned for modification 30 January 2002/ Accepted 26 March 2002

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.

* Corresponding author. Mailing address: Division of Bacterial, Parasitic and Allergenic Products, HFM-428, Center for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, MD 20852. Phone: (301) 496-2044. Fax: (301) 402-2776. E-mail: mbash{at}helix.nih.gov.

{dagger} This paper is dedicated to the memory of Major David Berry, M.D., Medical Corps, U.S. Army, who died in service to his country. Both his friendship and his contribution to the field of pediatric infectious diseases are sorely missed.

Editor: T. R. Kozel

Infection and Immunity, July 2002, p. 3707-3713, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3707-3713.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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