ANTIGENIC DETERMINANTS OF STAPHYLOCOCCUS-AUREUS TYPE-5 AND TYPE-8 CAPSULAR POLYSACCHARIDE VACCINES

Bacterial capsular polysaccharides (CP) are carbohydrate polymers comp rised of repeating saccharide units. Several of these CP have side cha ins attached to their backbone structures. The side chains may include O-acetyl, phosphate, sialic acid, and other moieties, Those moieties represent the immunodominant epitopes and the most functional ones. Th e clinically significant Staphylococcus aureus type 5 CP (CP 5) and ta pe 8 CP (CP 8) are comprised of a trisaccharide repeat unit with one O -acetyl group attached to each repeat unit. The immunogenicity of thes e CP and the functionality of antibodies to the backbone and the O-ace tyl moieties were investigated. Immunization with the native CP conjug ates (CP with 75% O-acetylation) elicited a high proportion of antibod ies directed against the O-acetyl moiety. Nonetheless, all of the vacc inees produced antibodies to the backbone moieties as well, Conjugate vaccines made of de-O-acetylated CP elicited backbone antibodies only. Antibodies to both backbone and O-acetyl groups were found to be opso nic against S. aureus strains which varied in their O-acetyl content. Absorption studies with O-acetylated and de-O-acetylated CP showed tha t (i) native CP conjugates generated antibodies to both backbone and O -acetyl groups and (ii) O-acetylated isolates mere opsonized by both p opulations of antibodies while the non-O-acetylated strains were predo minantly opsonized by the backbone antibodies, These results suggest t hat S. aureus CP conjugate vaccines elicit multiple populations of ant ibodies with diverse specificities. Moreover, the antibodies of differ ent specificities (backbone or O-acetyl) are all functional and effici ent against the variations in bacterial CP that may occur among clinic ally significant S. aureus pathogenic isolates.