A strategy for multivalent presentation of carba analogues from N. meningitidis A capsular polysaccharide

Neisseria meningitidis is a Gram-negative encapsulated bacterium that is a major cause of meningitis and meningococcal septicemia. Serogroup A (MenA) is most often implicated in epidemic disease in the sub-Saharan region of Africa. However, the development and manufacture of an efficient polysaccharide-based vaccine against MenA is greatly hampered by the poor immunogenicity and instability of its capsular polisaccharide (CPS). We report the synthesis of stable MenA CPS carba analogues, and an easy strategy to access multivalent carbohydrate structures based on iron oxide nanoparticles (SPIONs). A 1-O-tetraethyleneglycol-phosphate linker attached to the carba analogues was used to attach them to the metal surface. We evaluated the positive multivalent effect of the antigen presentation by MRI analysis, which showed that the conjugated monomer and dimer analogues could be recognised by the polyclonal anti-MenA antibody.