Bacterial polysaccharide-protein conjugate vaccines

The age-related and T-cell independent properties of polysaccharides limit their use as vaccines. These limitations are overcome by covalently binding polysaccharides to proteins to form conjugates. Widespread use of Haemophilus influenzae type b (Hib) conjugates has virtually eliminated systemic infection caused by this pathogen, notably meningitis, in individuals of all ages. The principles derived from the development and use of Hib conjugates have been applied to other capsulated pathogens including pneumococci and meningococci. We have shown that vaccine-induced serum IgG antibodies to the surface polysaccharides of enteric pathogens confer immunity to typhoid fever (Vi) and to S. sonnei. Our preliminary data show that synthetic saccharides provide a method for increasing the immunogenicity of conjugates and permitted more direct characterization of a S. dysenteriae type 1 conjugate. Both the chain length and density of the saccharides on the protein were related to the immunogenicity of conjugates in mice. A synthetic approach has also been extended to the LPS types of Vibrio cholerae O1.