A semisynthetic glycoconjugate provides expanded cross-serotype protection against Streptococcus pneumoniae

Paulina Kaplonek; Ling Yao; Katrin Reppe; Franziska Voß; Thomas Kohler; Friederike Ebner; Alexander Schäfer; Ulrike Blohm; Patricia Priegue; Maria Bräutigam; Claney L Pereira; Sharavathi G Parameswarappa; Madhu Emmadi; Petra Ménová; Martin Witzenrath; Sven Hammerschmidt; Susanne Hartmann; Leif E Sander; Peter H Seeberger

doi:10.1016/j.vaccine.2021.12.068

A semisynthetic glycoconjugate provides expanded cross-serotype protection against Streptococcus pneumoniae

Vaccine. 2022 Feb 11;40(7):1038-1046. doi: 10.1016/j.vaccine.2021.12.068. Epub 2022 Jan 13.

Authors

Paulina Kaplonek¹, Ling Yao², Katrin Reppe³, Franziska Voß⁴, Thomas Kohler⁴, Friederike Ebner⁵, Alexander Schäfer⁶, Ulrike Blohm⁶, Patricia Priegue⁷, Maria Bräutigam⁷, Claney L Pereira⁷, Sharavathi G Parameswarappa⁷, Madhu Emmadi⁷, Petra Ménová⁷, Martin Witzenrath⁸, Sven Hammerschmidt⁴, Susanne Hartmann⁵, Leif E Sander⁹, Peter H Seeberger¹⁰

Affiliations

¹ Max-Planck-Institute of Colloids and Interfaces, Department of Biomolecular Systems, Am Mühlenberg 1, 14476 Potsdam, Germany; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin, Germany.
² Max-Planck-Institute of Colloids and Interfaces, Department of Biomolecular Systems, Am Mühlenberg 1, 14476 Potsdam, Germany; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
³ Department of Infectious Diseases and Respiratory Medicine, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
⁴ Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, Germany.
⁵ Institute of Immunology, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
⁶ Institute of Immunology, Friedrich-Loeffler-Institut, Südufer 10, 17493 Greifswald-Insel Riems, Germany.
⁷ Max-Planck-Institute of Colloids and Interfaces, Department of Biomolecular Systems, Am Mühlenberg 1, 14476 Potsdam, Germany.
⁸ Department of Infectious Diseases and Respiratory Medicine, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; German Center for Lung Research (DZL), Aulweg 130, 35392 Giessen, Germany.
⁹ Department of Infectious Diseases and Respiratory Medicine, Charité - Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; German Center for Lung Research (DZL), Aulweg 130, 35392 Giessen, Germany. Electronic address: leif-erik.sander@charite.de.
¹⁰ Max-Planck-Institute of Colloids and Interfaces, Department of Biomolecular Systems, Am Mühlenberg 1, 14476 Potsdam, Germany; Freie Universität Berlin, Institute of Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin, Germany. Electronic address: peter.seeberger@mpikg.mpg.de.

PMID: 35033388
DOI: 10.1016/j.vaccine.2021.12.068

Abstract

Streptococcus pneumoniae (S. pneumoniae)infections are the leading cause of child mortality globally. Currentvaccines fail to induceaprotective immune response towards a conserved part of the pathogen,resulting in newserotypescausing disease. Therefore, new vaccinestrategies are urgently needed.Described is atwo-pronged approach combiningS. pneumoniaeproteins, pneumolysin (Ply) and pneumococcal surface protein A (PspA),with aprecisely defined synthetic oligosaccharide,wherebythe carrier protein actsas a serotype-independent antigen to provideadditional protection. Proof of concept in mice and swine modelsrevealed thatthe conjugatesinhibited colonization of the nasopharynx, decreased the bacterial load and reduced disease severity in the bacteria challenge model. Immunization of piglets provided the first evidence for the immunogenicity and protective potential of synthetic glycoconjugate vaccine in a large animal model.Acombination of synthetic oligosaccharides with proteins from the target pathogen opens the path to create broadly cross-protective ("universal") pneumococcal vaccines.

Keywords: Carbohydrate vaccines; Carrier protein; Infectious diseases; Streptococcus pneumoniae; Vaccines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Bacterial
Bacterial Proteins
Glycoconjugates
Mice
Pneumococcal Infections*
Pneumococcal Vaccines
Serogroup
Streptococcus pneumoniae*
Swine

Substances

Antibodies, Bacterial
Bacterial Proteins
Glycoconjugates
Pneumococcal Vaccines