Effect of various adjuvants on the antibody response of mice to pneumococcal polysaccharides.

: Adjuvant effects on the serum antibody response to pneumococcal polysaccharide (pps) types 3 and 14 were studied in BALB/c mice. First, dose responses were established for the two pps types and were found to be entirely different. High (5 micrograms) and low (0.005 microgram) doses of pps 3 induced antigen-specific unresponsiveness and suppression, while 0.1 microgram induced an optimal response. The secondary response to a single dose of killed pneumococci or 0.1 microgram of pps 3 injected 2 weeks later was not higher than the primary response. Nu/Nu, athymic BALB/c mice showed high but not low dose tolerance to pps 3. In contrast, no convincing evidence for high dose tolerance to pps 14 was obtained: 25 micrograms of pps 14 induced an optimal response, whereas 0.2-0.5 microgram induced antigen-specific suppression. Secondary anti-pps 14 IgM and IgG responses, even after optimal primary doses, were only slightly higher than primary responses to a single dose of killed bacteria. Athymic BALB/c mice showed lower IgG antibody responses than euthymic mice to pps 14. Injection of detoxified endotoxin (D-LPS) 2-4 days after antigen enhanced both primary and secondary responses and reversed high dose tolerance induction. Injection of D-LPS also at least partially prevented the induction of low dose tolerance as did injection of interleukin-1, but normuramyl dipeptide (nor-MDP) failed to affect the responses to pps 3 and 14. Coupling of muramyl tripeptide to pps 3 rendered the pps more immunogenic. Administration of emulsified pps in squalene arlacel, particularly with nor-MDP incorporated in the mixture, appeared to induce a better 7S antibody response than did pps in saline, but these serum antibody levels were not sustained at a high level. Pretreatment with IgD or simultaneous injection of IgD with pps 14 enhanced both primary and secondary responses. The response to pps 3 was only slightly enhanced and low dose tolerance was not prevented by pretreatment with IgD.