Preparation, antigenicity, and immunogenicity of synthetic ribosylribitol phosphate oligomer-protein conjugates and their potential use for vaccination against Haemophilus influenzae type b disease.
Synthetically prepared ribosylribitol phosphate dimer and trimer analogous to fragments of the capsular polysaccharide of Haemophilus influenzae type b, containing either an amino- or a (masked) thiol-functionalized spacer, were conjugated to protein by two different methods. The thiol-containing carbohydrates were conjugated to tetanus toxoid or H. influenzae outer membrane protein using N-succinimidyl 3-(2-pyridyldithio)propionate. Glutaric dialdehyde was used to conjugate the amino-containing carbohydrates with tetanus toxoid. All conjugates were able to bind antibodies raised against the native bacterial polysaccharide, as determined by competition ELISA. The glutaric dialdehyde conjugate prepared from ribosylribitol phosphate trimer and tetanus toxoid induced a strong polysaccharide-specific antibody response in mice and rabbits.
Evenberg
D
D
Laboratory of Bacterial Vaccines, National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands.
Hoogerhout
P
P
van Boeckel
C A
CA
Rijkers
G T
GT
Beuvery
E C
EC
van Boom
J H
JH
Poolman
J T
JT
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000032:analysis*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D006192:Haemophilus Infections / Q000517:prevention & control; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000276:immunology*; D051379:Mice; D008970:Molecular Weight; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D013745:Tetanus Toxoid / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; C061964:Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic