Abstract
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 Statement
European 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.