Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection

Vaccines

ThomasH. A. Ederveen¹  Franziska Voß²  Sven Hammerschmidt²  Daniela Thalheim²  Sidney Werner²  Dominik Schwudke³  MarienI. de Jonge⁴  LucilleF. van Beek⁴  FredJ. van Opzeeland⁴ 

[1] Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;Department 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;Division of Bioanalytical Chemistry, Priority Area Infection, Research Center Borstel, Leibniz Center for Medicine and Bioscience, 23845 Borstel, Germany;Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands;

关键词: Streptococcus pneumoniae;    lipoproteins;    lipidation;    pneumococcal colonization;    vaccine;    protection;   

DOI  :  10.3390/vaccines8020310

来源: DOAJ

【 摘 要 】

Streptococcus pneumoniae 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 S. pneumoniae 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.

【 授权许可】

Unknown