EPITOPE SPECIFICITY OF RABBIT IMMUNOGLOBULIN-G (IGG) ELICITED BY PNEUMOCOCCAL TYPE 23F SYNTHETIC OLIGOSACCHARIDE-PROTEIN AND NATIVE POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES - COMPARISON WITH HUMAN ANTI-POLYSACCHARIDE 23F IGG

Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) cons ists of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigat ed: (i) a synthetic trisaccharide comprising the backbone of one repea ting unit, (ii) a synthetic tetrasaccharide comprising the complete re peating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. A ll antigens except the trisaccharide-KLH conjugate induced relatively high anti-PS23F antibody levels in rabbits. The epitope specificity of such antibodies was then studied by means of an inhibition immunoassa y. The cw(1-->2)-linked L-rhamnose branch was shown to be immunodomina nt for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KL H, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhib ited the binding of IgG to PS23F. Thus, there appears to be no major d ifference in epitope specificity between IgG induced by tetrasaccharid e-KLH and that induced by antigens containing the polymeric form of PS 23F. Human anti-PS23F IgG (either vaccine induced or naturally acquire d) had a different epitope specificity: none of the inhibitors used, i ncluding L-rhamnose and tetrasaccharide-KLH, exhibited substantial inh ibition. These observations suggest that the epitope recognized by hum an IgG on PS23F is larger than the epitope recognized by rabbit IgG. B oth human and rabbit antisera efficiently opsonized type 23F pneumococ ci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes.