RT Journal Article
SR Electronic
T1 A semisynthetic glycoconjugate provides expanded cross-serotype protection against <em>Streptococcus pneumoniae</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.29.454378
DO 10.1101/2021.07.29.454378
A1 Paulina Kaplonek
A1 Ling Yao
A1 Katrin Reppe
A1 Franziska Voß
A1 Thomas Kohler
A1 Friederike Ebner
A1 Alexander Schäfer
A1 Ulrike Blohm
A1 Patricia Priegue
A1 Maria Bräutigam
A1 Claney L. Pereira
A1 Sharavathi G. Parameswarappa
A1 Madhu Emmadi
A1 Petra Ménová
A1 Martin Witzenrath
A1 Sven Hammerschmidt
A1 Susanne Hartmann
A1 Leif E. Sander
A1 Peter H. Seeberger
YR 2021
UL http://biorxiv.org/content/early/2021/07/30/2021.07.29.454378.abstract
AB Streptococcus 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 and 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 inhibit colonization of the nasopharynx, decrease the bacterial load and reduce disease severity in the bacteria challenged 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.Competing Interest StatementEuropean Patent Application No. EP 20 170 605.8; Synthetic Streptococcus pneumoniae saccharide conjugates to conserved membrane protein filed by the inventors P.H.S., L.E.S., P.K. and S.V.H. Glycoconjugates containing the synthetic glycan structures of Streptococcus pneumoniae serotypes serotype 2 and 3 are included in patent "Pneumococcal oligosaccharide-protein conjugate composition" no. EP 16 179 133.0 filed by the inventors P.H.S. and P.K.