Synthetic polysaccharide type 3-related di-, tri-, and tetrasaccharide-CRM197 conjugates induce protection against Streptococcus pneumoniae type 3 inmice

Di-, tri-, and tetrasaccharides, synthesized according to the chemical stru cture of pneumococcal polysaccharide type 3 (PS3), were coupled to the cros s-reactive material (CRM197) of modified diphtheria toxin in different mola r carbohydrate/protein ratios using the squarate coupling method. To study protective immunity, female BALB/c mice were subcutaneously immunized twice (with a 3-week interval) using the amount of conjugates corresponding to 2 .5 mug of oligosaccharide per mouse. The conjugates evoked PS3 binding immu noglobulin G antibodies that lasted for at least 7 weeks after the booster. Immunogenicity was not influenced by the carbohydrate/protein ratio. All m ice with PS3-specific antibodies survived the intraperitoneal challenge wit h Streptococcus pneumoniae type 3, Therefore, synthetic oligosaccharide-pro tein conjugates might have potential as vaccines.