ANTIBODY-RESPONSES TO CAPSULAR POLYSACCHARIDE BACKBONE AND O-ACETATE SIDE-GROUPS OF STREPTOCOCCUS-PNEUMONIAE TYPE 9V IN HUMANS AND RHESUS MACAQUES

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 po lysaccharide (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 capsu le consists of repeating pentasaccharide units linearly arranged, with an average of 1 to 2 mol of O-acetate side chains per mol of repeat u nits, added in a complex pattern in which not all repeat units are ali ke. 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-acetylatio n of a significant number of the repeat units. This de-O-acetylation c ould adversely affect the efficacy of a vaccine containing the 9V Ps, A study was undertaken to compare the relative contributions of O-acet ate and Ps backbone epitopes in the immune response to S. pneumoniae 9 V 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) activ ity was observed in antisera in which the predominant species of antib ody 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.