Towards a novel synthetic Streptococcus pneumoniae vaccine

In a multidisciplinary collaborative work between the Leiden Institute of Chemistry (The Netherlands), the Amsterdam Infection and Immunity Institute (Amsterdam), the Finlay Vaccine Institute (Havana, Cuba) and CIC bioGUNE (Derio), the topology and minimal epitope of the zwitterionic Streptococcus pneumoniae serotype 1 polysaccharide (Sp1) have been unraveled. Synthetic fragments, with different sizes, of the natural polysaccharide, which is an important anchor point for our immune system to act against streptococcal infections, have been synthesized at Leiden and their three-dimensional structures and their serum and antibody binding features have been deduced at CIC bioGUNE by NMR. The recognition process is length dependent and requires a helical shape, as measured using competitive ELISA methods at Amsterdam and Havana and by NMR at Derio. A nonasaccharide is postulated as a very attractive candidate for the generation of an anti-Sp1 vaccine modality.

Qingju Zhang, Ana Gimeno, Darielys Santana, Zhen Wang, Yury Valdes-Balbin,
Laura M. Rodriguez-Noda, Thomas Hansen, Li Kong, Mengjie Shen, Herman S. Overkleeft,  Vicente Verez-Bencomo, Gijsbert A. van der Marel, Jesus Jimenez-Barbero,  Fabrizio Chiodo,  Jeroen D. C. Codée

Synthetic, Zwitterionic Sp1 Oligosaccharides Adopt a Helical Structure Crucial for Antibody Interaction

ACS Cent. Sci. 2019, 5, 1407-1416

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