Synthetic polysaccharide type 3-related di-, tri-, and tetrasaccharide-CRM(197) conjugates induce protection against Streptococcus pneumoniae type 3 in mice.
Di-, tri-, and tetrasaccharides, synthesized according to the chemical structure of pneumococcal polysaccharide type 3 (PS3), were coupled to the cross-reactive material (CRM(197)) of modified diphtheria toxin in different molar 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 microg of oligosaccharide per mouse. The conjugates evoked PS3 binding immunoglobulin G antibodies that lasted for at least 7 weeks after the booster. Immunogenicity was not influenced by the carbohydrate/protein ratio. All mice with PS3-specific antibodies survived the intraperitoneal challenge with Streptococcus pneumoniae type 3. Therefore, synthetic oligosaccharide-protein conjugates might have potential as vaccines.
Benaissa-Trouw
B
B
Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, Utrecht, The Netherlands. B.J.BenaissaTrouw@lab.azu.nl
Lefeber
D J
DJ
Kamerling
J P
JP
Vliegenthart
J F
JF
Kraaijeveld
K
K
Snippe
H
H
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002240:Carbohydrate Sequence; D003429:Cross Reactions; D004167:Diphtheria Toxin / Q000276:immunology*; D004187:Disaccharides / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D014312:Trisaccharides / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004167:Diphtheria Toxin; D004187:Disaccharides; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D014312:Trisaccharides; C026604:pneumococcal polysaccharide, type III; C028581:CRM197 (non-toxic variant of diphtheria toxin)