TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Voß, Franziska A1 - van Beek, Lucille F. A1 - Schwudke, Dominik A1 - Ederveen, Thomas H. A. A1 - van Opzeeland, Fred J. A1 - Thalheim, Daniela A1 - Werner, Sidney A1 - de Jonge, Marien I. A1 - Hammerschmidt, Sven T1 - Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection JF - Vaccines N2 - Streptococcus pneumoniaeinfections lead to high morbidity and mortality rates worldwide.Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but havea limited range of protection, which encourages the development of a broadly protective protein-basedalternative. We and others have shown that immunization with pneumococcal lipoproteins that lackthe lipid anchor protects against colonization. Since immunity againstS. pneumoniaeis mediatedthrough Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects ofa lipid modification on the induced immune responses in either intranasally or subcutaneouslyvaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrAstrongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhancedantibody concentrations and different induction kinetics. The induced humoral immune responsewas modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-typeimmunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderatebut consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins,indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus,protein lipidation represents a promising approach for the development of a serotype-independentpneumococcal vaccine. KW - - KW - Streptococcus pneumoniae KW - lipoproteins KW - lipidation KW - pneumococcal colonization KW - vaccine KW - protection KW - immune response Y1 - 2020 UN - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-38456 SN - 2076-393X SS - 2076-393X U6 - https://doi.org/https://doi.org/10.3390/vaccines8020310 DO - https://doi.org/https://doi.org/10.3390/vaccines8020310 VL - 8 IS - 2 SP - 310 PB - MDPI CY - Basel ER -