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Bitte verwenden Sie diesen Link, wenn Sie dieses Dokument zitieren oder verlinken wollen: https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-38456

Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection

  • 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.

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Metadaten
Author: Franziska Voß, Lucille F. van Beek, Dominik Schwudke, Thomas H. A. Ederveen, Fred J. van Opzeeland, Daniela Thalheim, Sidney Werner, Marien I. de Jonge, Sven Hammerschmidt
URN:urn:nbn:de:gbv:9-opus-38456
DOI:https://doi.org/https://doi.org/10.3390/vaccines8020310
ISSN:2076-393X
Parent Title (English):Vaccines
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of first Publication:2020/06/17
Release Date:2020/10/17
Tag:<i>Streptococcus pneumoniae</i>; immune response; lipidation; lipoproteins; pneumococcal colonization; protection; vaccine
GND Keyword:-
Volume:8
Issue:2
First Page:310
Faculties:Mathematisch-Naturwissenschaftliche Fakultät / Abteilung für Mikrobiologie und Molekularbiologie
Collections:Artikel aus DFG-gefördertem Publikationsfonds
Licence (German):License LogoCreative Commons - Namensnennung