Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal type 23F synthetic oligosaccharide- and native polysaccharide-protein conjugate vaccines: comparison with human anti-polysaccharide 23F IgG.
Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigated: (i) a synthetic trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. All 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 immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the binding of IgG to PS23F. Thus, there appears to be no major difference in epitope specificity between IgG induced by tetrasaccharide-KLH and that induced by antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either vaccine induced or naturally acquired) had a different epitope specificity: none of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited substantial inhibition. These observations suggest that the epitope recognized by human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes.
Alonso de Velasco
E
E
Eijkman-Winkler Laboratory of Medical Microbiology, Utrecht University, The Netherlands.
Verheul
A F
AF
van Steijn
A M
AM
Dekker
H A
HA
Feldman
R G
RG
Fernández
I M
IM
Kamerling
J P
JP
Vliegenthart
J F
JF
Verhoef
J
J
Snippe
H
H
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D002240:Carbohydrate Sequence; D000939:Epitopes; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000276:immunology; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D000939:Epitopes; D007074:Immunoglobulin G; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate