Design, preparazione e valutazione biologica di una piccola collezione di composti contenenti il disaccaride comune alle capsule polisaccaridiche di Streptococcus pneumoniae 19F e 19A

Pneumonia is one of the most serious respiratory infection worldwide, and it is mainly caused by Streptococcus pneumoniae (SP) bacterium. Since the polysaccharide capsule of SP is a major virulence factor, commercially available vaccines are made of the most virulent polysaccharide serotypes. The World Health Organization recommends pneumococcal vaccination for children younger than 2 years of age, adults 65 years and older and people with impaired medical conditions. Pneumococcal conjugate vaccines (PCVs) work well and, even if they are not able to prevent all infections, they have substantially reduced the incidence of invasive pneumococcal disease caused by the most common vaccine serotypes. However, serotype replacement with non-PCV serogroups remains a concern and we are still distant from achieving a universal not serotype-dependent vaccine. We envisioned to simplify PCV formulations designing novel non-natural saccharide antigens common to more than one serotype. In this context, we envisaged a potential antigen composed of common structures shared by different serotypes. In particular, SP 19F and 19A repeating units share a common structure, the disaccharide ManNAc-β-(14)-Glc, that can be considered the parent motif for the selection of a “common epitope”. Accordingly, we have synthesized a small library of compounds, containing different combinations of the common 19F/19A disaccharide. Each fragment, bearing an aminopropyl spacer at the reducing end to allow the multivalent presentation by conjugation to different scaffolds, will be biologically evaluated through glycan-arrays screening to reveal the presence of common antibodies protective both for 19F and 19A serotypes.