EFFECT OF OLIGOSACCHARIDE (OS) CHAIN LENGTH, TERMINAL GROUP, AND HAPTEN LOADING ON THE SERUM ANTIBODY (Ab) RESPONSE OF 1-YR-OLD INFANTS TO H. INFLUENZAE B CAPSULAR ANTIGEN (PRP) CONJUGATED TO THE DIPHTHERIA PROTEIN CRM197

Abstract

Vaccines consisting of OS derived from PRP and conjugated by reductive amination to the nontoxic diphtheria mutant toxin CRM 197 (C) were previously shown to elicit memory-type serum anti-PRP responses in human infants. Here we seek to define structural variables that control the infant's response. In the coupled OS, the nonreducing (and hence exposed) terminal group can be ribitol (r), ribose (R), or phosphate (p). A series of r-terminal OS of mean length 4, 6, or 12 repeat units were coupled to C at ca. 10 ribose/protein, and OS of 12 repeat units terminating in R or p were coupled at ca. 30 ribose/protein. A 2-injection sequence was given to healthy infants aged 9-15 mo (groups of 8-10). Anti-PRP Ab was assayed by radioantigen binding; at 1 mo after the 2° the geometric means (GM) and 95% confidence intervals (CI) were:

Series C4r, C6r, C12r (all at low hapten loading) induced similar titers regardless of OS chain length. C12R and C12p (both with high loadings) induced similar titers that were >10-fold the r series.

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