6.1.5 Conjugate vaccines: Linking carbohydrates to proteins
The use of bioconjugates for the development of vaccines is a common strategy. This is most
critical for antigens that may be hard to generate synthetically. The best example is likely the
polysaccharides produced by bacteria. These polysaccharides are often unique to certain species
and distinct from human saccharides, providing a selective antigen for use in a vaccine. Reviews
of glyconjugate vaccines discuss specific issues related to the selection of antigens and
generation of a successful vaccine conjugate.
The first glycoconjugate vaccine was reported by Avery & Goedel in 1931, in which they
conjugated the polysaccharide of pneumococcus to proteins. 39, 4Their strategy exploited non-
specific reaction of hydroxyl groups on the polysaccharide, converting them to diazo groups
using a benzyl linker. The diazo group could then react with Tyr residues of the protein to
generate a stable linkage. The use of diazo chemistry to specif ically modify Tyr or Trp residues
has since been developed as a more specific protein-modification strategy.
The development of the conjugate vaccine for meningococcal infections was reported in 1981
by researchers at the National Research Council of Canada. 42, 4The chemistry used involved
isolation of the capsular polysaccharide (CPS) from the bacteria, followed by its conjugation
using either reductive amination or sodium periodate chemistry. 43 The meningococcal CPS
235 BioconjugateChemistry Cairo
contains a poly-sialic acid, which allows selective oxidation of the terminal sialic acid. The CPS
polysaccharide is then conjugated to an immunogenic protein. The protein used here was the
tetanus toxoid protein (TT).
HO OH COO - COO-