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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Streptococcus pneumoniae (S. pneumoniae) infections are the leading cause of child mortality globally. Current vaccines fail to induce a protective immune response towards a conserved part of the pathogen, resulting in new serotypes causing disease. Therefore, new vaccine strategies are urgently needed. Described is a two-pronged approach combining S. pneumoniae proteins, pneumolysin (Ply) and pneumococcal surface protein A (PspA), with a precisely defined synthetic oligosaccharide, whereby the carrier protein acts as a serotype-independent antigen to provide additional protection. Proof of concept in mice and swine models revealed that the conjugates inhibited 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. A combination of synthetic oligosaccharides with proteins from the target pathogen opens the path to create broadly cross-protective (“universal”) pneumococcal vaccines.

Original languageEnglish
Pages (from-to)1038-1046
Number of pages9
JournalVaccine
Volume40
Issue number7
DOIs
StatePublished - 11 Feb 2022
Externally publishedYes

Keywords

  • Carbohydrate vaccines
  • Carrier protein
  • Infectious diseases
  • Streptococcus pneumoniae
  • Vaccines

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