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ACS Cent Sci. 2018 Mar 28;4(3):357-361. doi: 10.1021/acscentsci.7b00504. Epub 2018 Mar 14.

Development of an Efficacious, Semisynthetic Glycoconjugate Vaccine Candidate against Streptococcus pneumoniae Serotype 1.

Author information

1
Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
2
Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
3
Division of Pulmonary Inflammation, Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.

Abstract

Infections with Streptococcus pneumoniae are a major health burden. Glycoconjugate vaccines based on capsular polysaccharides (CPSs) successfully protect from infection, but not all pneumococcal serotypes are covered with equal potency. Marketed glycoconjugate vaccines induce low levels of functional antibodies against the highly invasive serotype 1 (ST1), presumably due to the obscuring of protective epitopes during chemical activation and conjugation to carrier proteins. Synthetic oligosaccharide antigens can be designed to carry linkers for site-selective protein conjugation while keeping protective epitopes intact. Here, we developed an efficacious semisynthetic ST1 glycoconjugate vaccine candidate. A panel of synthetic oligosaccharides served to reveal a critical role of the rare aminosugar, 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (d-AAT), for ST1 immune recognition. A monovalent ST1 trisaccharide carrying d-AAT at the nonreducing end induced a strong antibacterial immune response in rabbits and outperformed the ST1 component of the multivalent blockbuster vaccine Prevenar 13, paving the way for a more efficacious vaccine.

Conflict of interest statement

The authors declare the following competing financial interest(s): This work has been the subject of the patent Synthetic vaccines against Streptococcus pneumoniae, PCT/EP2014/064407, held by the Max Planck Gesellschaft zur Förderung der Wissenschaften e.V. covering synthetic ST1 saccharides. B.S. is an inventor on said patent. C.L.P. is an inventor on said patent and has a significant financial interest in Vaxxilon AG, a company that is developing semisynthetic glycoconjugate vaccines and has exclusively licensed the patent stated above. He is an employee of the German daughter company of Vaxxilon AG called Vaxxilon Deutschland GmbH and has Phantom Stock Options in the parent company. C.A. is an inventor on the patent stated above. P.H.S. is an inventor on the patent stated above and has a significant financial interest in Vaxxilon AG. He is the scientific founder, a member of the board, and a shareholder and acts as a consultant for Vaxxilon AG. K.R., A.W., P.K., and M.W. declare no relevant competing interests.

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