Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection
<i>Streptococcus pneumoniae</i> infections lead to high morbidity and mortality rates worldwide. Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but have a limited range of protection, which encourages the development of a broadly protective prot...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/2/310 |
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| 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 |
| author_facet | 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 |
| author_sort | Franziska Voß |
| collection | DOAJ |
| description | <i>Streptococcus pneumoniae</i> infections lead to high morbidity and mortality rates worldwide. Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but have a limited range of protection, which encourages the development of a broadly protective protein-based alternative. We and others have shown that immunization with pneumococcal lipoproteins that lack the lipid anchor protects against colonization. Since immunity against <i>S. pneumoniae</i> is mediated through Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects of a lipid modification on the induced immune responses in either intranasally or subcutaneously vaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrA strongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhanced antibody concentrations and different induction kinetics. The induced humoral immune response was modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-type immunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderate but 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-independent pneumococcal vaccine. |
| first_indexed | 2024-03-10T19:07:29Z |
| format | Article |
| id | doaj.art-d7bc99e9b9c94b5bb3271c7795d820da |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T19:07:29Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d7bc99e9b9c94b5bb3271c7795d820da2023-11-20T04:05:39ZengMDPI AGVaccines2076-393X2020-06-018231010.3390/vaccines8020310Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and ProtectionFranziska Voß0Lucille F. van Beek1Dominik Schwudke2Thomas H. A. Ederveen3Fred J. van Opzeeland4Daniela Thalheim5Sidney Werner6Marien I. de Jonge7Sven Hammerschmidt8Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, GermanySection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The NetherlandsDivision of Bioanalytical Chemistry, Priority Area Infection, Research Center Borstel, Leibniz Center for Medicine and Bioscience, 23845 Borstel, GermanyCenter for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The NetherlandsDepartment of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, GermanyDepartment of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, GermanySection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The NetherlandsDepartment of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany<i>Streptococcus pneumoniae</i> infections lead to high morbidity and mortality rates worldwide. Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but have a limited range of protection, which encourages the development of a broadly protective protein-based alternative. We and others have shown that immunization with pneumococcal lipoproteins that lack the lipid anchor protects against colonization. Since immunity against <i>S. pneumoniae</i> is mediated through Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects of a lipid modification on the induced immune responses in either intranasally or subcutaneously vaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrA strongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhanced antibody concentrations and different induction kinetics. The induced humoral immune response was modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-type immunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderate but 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-independent pneumococcal vaccine.https://www.mdpi.com/2076-393X/8/2/310<i>Streptococcus pneumoniae</i>lipoproteinslipidationpneumococcal colonizationvaccineprotection |
| spellingShingle | 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 Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection Vaccines <i>Streptococcus pneumoniae</i> lipoproteins lipidation pneumococcal colonization vaccine protection |
| title | Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection |
| title_full | Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection |
| title_fullStr | Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection |
| title_full_unstemmed | Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection |
| title_short | Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection |
| title_sort | lipidation of pneumococcal antigens leads to improved immunogenicity and protection |
| topic | <i>Streptococcus pneumoniae</i> lipoproteins lipidation pneumococcal colonization vaccine protection |
| url | https://www.mdpi.com/2076-393X/8/2/310 |
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