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Infect Immun, August 1998, p. 3705-3710, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Antibody Responses to Capsular Polysaccharide Backbone and O-Acetate Side Groups of Streptococcus pneumoniae Type 9V in Humans and Rhesus Macaques

Tessie B. McNeely,1 Joan M. Staub,1 Cynthia M. Rusk,1 Michael J. Blum,2 and John J. Donnelly1 *

Departments of Virus and Cell Biology1 and Clinical Research,2 Merck Research Laboratories, West Point, Pennsylvania

Received 13 February 1998/Returned for modification 14 April 1998/Accepted 1 May 1998

Streptococcus pneumoniae is responsible for high rates of pneumococcal bacteremia, meningitis, pneumonia, and acute otitis media worldwide. Protection from disease is conferred by antibodies specific for the polysaccharide (Ps) capsule of the bacteria. Of the four types of group 9 pneumococci, types 9N and 9V cause the most disease, and both types are included in the polyvalent pneumococcal vaccine. The type 9V capsule consists of repeating pentasaccharide units linearly arranged, with an average of 1 to 2 mol of O-acetate side chains per mol of repeat units, added in a complex pattern in which not all repeat units are alike. alpha -GlcA residues may be O-acetylated in the 2 (17%) or 3 (25%) position and beta -ManNAc residues may be O-acetylated in the 4 (6%) or 6 (55%) position. Under certain conditions, the O-acetate side chains are subject to oxidation, which results in subsequent de-O-acetylation of a significant number of the repeat units. This de-O-acetylation could adversely affect the efficacy of a vaccine containing the 9V Ps. A study was undertaken to compare the relative contributions of O-acetate and Ps backbone epitopes in the immune response to S. pneumoniae 9V type-specific Ps. In both an infant rhesus monkey model and humans, antibodies against the non-O-acetylated 9V backbone as well as against O-acetylated 9V Ps were detected. Functional (opsonophagocytic) activity was observed in antisera in which the predominant species of antibody recognized de-O-acetylated 9V Ps. We concluded that the O-acetate side groups, while recognized, are not essential to the ability of the 9V Ps to induce functional antibody responses.

* Corresponding author. Mailing address: Merck Research Laboratories, P.O. Box 4, WP26-253, West Point, PA 19486. Phone: (215) 652-3683. Fax: (215) 652-8127. E-mail: john_donnelly{at}merck.com.

Infect Immun, August 1998, p. 3705-3710, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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