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Clinical and Vaccine Immunology, May 2007, p. 577-584, Vol. 14, No. 5
1071-412X/07/$08.00+0     doi:10.1128/CVI.00009-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Protective Meningococcal Capsular Polysaccharide Epitopes and the Role of O Acetylation

Peter C. Fusco,^* Esmé K. Farley, Chun-Hsien Huang, Samuel Moore, and Francis Michon^*

BioVeris Corporation, 16020 Industrial Dr., Gaithersburg, Maryland 20877

Received 4 January 2007/ Returned for modification 30 January 2007/ Accepted 12 February 2007

Previous studies with group C meningococcal polysaccharide-tetanus toxoid (GCMP-TT) conjugates had suggested that the GCMP O-acetyl group masked the protective epitope for group C meningococci through steric hindrance or altered conformations. For this report, we confirmed this phenomenon and performed comparative studies with group Y meningococcal polysaccharide (GYMP)-TT to determine whether it might extend to other serogroups. The de-O-acetylated (dOA) polysaccharides (PSs) resulted in higher serum bactericidal activities (SBA) towards the O-acetylated (OA) meningococcal strains from the respective serogroups. High-resolution H-nuclear magnetic resonance spectroscopy at 500 MHz and competitive inhibition serum bactericidal assays were used to characterize the nature of the protective epitope. In head-to-head comparisons with OA PSs as SBA inhibitors, the dOA PSs provided 10 to 1,000 times better inhibition for GCMP in human and mouse antisera and 6 to 13 times better inhibition for GYMP in mouse antisera, using OA strains in all assays. In addition, the SBA for OA strains was highly correlated with dOA PS-specific immunoglobulin G (r = 0.72 to 0.98) for both GCMP and GYMP. The results suggest that there may be a generalized role for the O-acetyl group to provide an epitope of misdirected immunogenicity for meningococcal PS capsules, enabling escape from immune surveillance. In addition to greater chemical consistency, the dOA forms of GCMP and GYMP conjugate vaccines endow greater immunologic competence to the PSs, rendering them capable of eliciting higher levels of functional antibodies toward the protective epitopes.

Published ahead of print on 21 March 2007.

Present address: Bridge Global Pharmaceutical Services, Inc., 610 Professional Dr., Gaithersburg, MD 20879.

This article has been cited by other articles:

• Moore, S. L., Uitz, C., Ling, C.-C., Bundle, D. R., Fusco, P. C., Michon, F. (2007). Epitope Specificities of the Group Y and W-135 Polysaccharides of Neisseria meningitidis. CVI 14: 1311-1317 [Abstract] [Full Text]  
• Rajam, G., Carlone, G. M., Romero-Steiner, S. (2007). Functional Antibodies to the O-Acetylated Pneumococcal Serotype 15B Capsular Polysaccharide Have Low Cross-Reactivities with Serotype 15C. CVI 14: 1223-1227 [Abstract] [Full Text]