Skip to main content

Chemoenzymatic synthesis of immunoreactive polysialic acid-tetanus Hc fragment glycoconjugates

Monday, October 24, 2011 — Poster Session I

Noon – 2:00 p.m.

Natcher Conference Center




  • PC McCarthy
  • R Saksena
  • C Lee
  • Y An
  • DC Peterson
  • JF Cipollo
  • WF Vann


Neisseria meningitidis serogroup C is one of the most common causes of meningitis in adolescents and adults in the United States. Currently licensed glycoconjugate vaccines, composed of acidic capsular polysaccharides conjugated to a carrier protein, have been proven safe and effective in these populations. However, the chemical methods used to generate such vaccines results in heterogeneous mixtures. Well-defined vaccines are needed to elucidate the relationship between vaccine structure and generated immune response. Here, we describe our efforts to produce these types of structures using chemoenzymatic synthesis. Chemically synthesized lactosides, containing azido groups at the aglycon were used as substrates for recombinant sialyltransferase enzymes from Camplyobacter jejuni and Neisseria meningitidis serogroup C. These azido-containing oligosialic acids, with the same repeat structure as the polysaccharide capsule of Neisseria, were then conjugated to alkyne-modified Hc fragment of the tetanus toxin protein using the “click” chemistry method of 1,3-cycloaddition. Chemoenzymatically prepared glycoconjugates were immunoreactive to antibodies against group C polysaccharide and Hc fragment protein in vitro. In vivo results indicated higher levels of polysaccharide-reactive IgG present in the serum of mice immunized with the glycoconjugates compared to those receiving unconjugated oligosaccharides. Chemoenzymatic synthesis may provide a viable method for making defined meningococcal vaccine candidates.

back to top