Abstract
The basis for the impaired antibody (Ab) response of young children to polysaccharide antigens (Ag) is unexplained. A series of dinitrophenyl (DNP)-substituted polyacrylamide (PA) molecules was synthesized to allow comparison of molecular requirements for immunogenicity of polysaccharide-like (T-independent) Ags in young vs adult mice (1-12 wks old). Three DNP-PA Ags were studied which varied in mol. wt. (60, 430, 2000 kD) but had similar hapten density (1 DNP/50 PA monomers). Dose-response relationships and kinetics of both IgM and IgG anti-DNP Ab responses were measured. We conclude that: (a) 60 kD DNP-PA was not immunogenic at any dose in any mouse, (b) Ab responses to 430 kD DNP-PA increased with age up to 10-12 wks when adult maximum levels were achieved, (c) 2000 kD DNP-PA was more immunogenic in every age group than 430 kD DNP-PA. In fact, the response to the 2000 kD polymer in 5 wk old mice was equivalent to the maximum adult response to the 430 kD polymer, (d) 60 kD DNP-PA inhibited the response to optimally immunogenic doses of 430 kD Ags. Inhibition was greatest in youngest mice.
These studies suggest that one strategy to improve immunogenicity of polysaccharide vaccines in young children might involve selective depletion of smaller mol. wt. material (< 100 kD) and/or selective enrichment of large mol. wt. material (> 1000kD) (Supported by grants from NIH and American Lung Association.)
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Lederman, H., Bergstrom, S., Dintzis, R. et al. MOLECULAR DETERMINANTS OF IMMUNOGENICITY OF T-INDEPENDENT ANTIGENS IN YOUNG MICE. Pediatr Res 21 (Suppl 4), 313 (1987). https://doi.org/10.1203/00006450-198704010-00877
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DOI: https://doi.org/10.1203/00006450-198704010-00877