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

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 patho-gen, 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 pneumo-coccal 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 pro-vided the first evidence for the immunogenicity and protective potential of synthetic glycoconjugate vac-cine 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. (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

Streptococcus pneumoniae infections are a major cause of child mortality worldwide. Current vaccines are ineffective in providing adequate protection, leading to new disease-causing serotypes. This study presents a two-pronged vaccine approach combining S. pneumoniae proteins with a synthetic oligosaccharide, which successfully inhibits colonization and reduces disease severity. This opens up possibilities for the development of broadly cross-protective pneumococcal vaccines.