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Vaccines based on isolated polysaccharides successfully protect humans from bacterial pathogens such as Streptococcus pneumoniae. Because polysaccharide production and isolation can be technically challenging, glycoconjugates containing synthetic antigens are an attractive alternative. Typically, the shortest possible oligosaccharide antigen is preferable as syntheses of longer structures are more difficult and time-consuming. Combining several protective epitopes or polysaccharide repeating units as blocks by bonds other than glycosidic linkages would greatly reduce the synthetic effort if the immunological response to the polysaccharide could be retained. To explore this concept, we bridged the well-understood and immunologically potent RU of S. pneumoniae serotype 14 (ST14) with an aliphatic spacer and conjugated it to the carrier protein CRM197. Mice immunized with the spacer-bridged glycan conjugates produced high levels of specific antibodies after just one or two vaccine doses, while the tetrasaccharide repeating unit alone required three doses. The antibodies recognized specifically ST14 CPS, while no significant antibody levels were raised against the spacer or unrelated CPS. Synthetic vaccines generated antibodies with opsonic activity. Mimicking polysaccharides by coupling repeating unit antigens via an aliphatic spacer may prove useful also for the development of other glycoconjugate vaccine candidates, thereby reducing the synthetic complexity while enhancing a faster immune response.

structure, Streptococcus pneumoniae, capsular polysaccharides, glycosidic linkage, antibodies, epitope, mice, protein, Synthetic, immune response, conjugates, carrier, glycoconjugate vaccine

NCBI PubMed ID: 32835479
Publication DOI: 10.1021/acschembio.0c00360
Journal NLM ID: 101282906
Publisher: Washington, DC: American Chemical Society
Correspondence: peter.seeberger

mpikg.mpg.de
Institutions: Department of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany, Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany, Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
Methods: 13C NMR, 1H NMR, SDS-PAGE, TLC, ELISA, chemical synthesis, MALDI-TOF MS, MD simulations, molecular modeling, immunization, conjugation, HR-ESI-MS