Next Article in Journal
Innate Lymphocyte Th1 and Th17 Responses in Elderly Hospitalised Patients with Infection and Sepsis
Previous Article in Journal
Vaccines against Coronaviruses: The State of the Art
Open AccessArticle

Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection

1
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
2
Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands
3
Radboud Center for Infectious Diseases, Radboudumc, 6525 GA Nijmegen, The Netherlands
4
Division of Bioanalytical Chemistry, Priority Area Infection, Research Center Borstel, Leibniz Center for Medicine and Bioscience, 23845 Borstel, Germany
5
German Center for Infection Research (DZIF), 38124 Braunschweig, Germany
6
Airway Research Center North Member of the German Center for Lung Research (DZL), 22927 Großhansdorf, Germany
7
Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These senior authors contributed equally to this work.
Vaccines 2020, 8(2), 310; https://doi.org/10.3390/vaccines8020310
Received: 9 April 2020 / Revised: 4 May 2020 / Accepted: 11 June 2020 / Published: 17 June 2020
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. View Full-Text
Keywords: Streptococcus pneumoniae; lipoproteins; lipidation; pneumococcal colonization; vaccine; protection; immune response Streptococcus pneumoniae; lipoproteins; lipidation; pneumococcal colonization; vaccine; protection; immune response
Show Figures

Figure 1

MDPI and ACS Style

Voß, F.; van Beek, L.F.; Schwudke, D.; Ederveen, T.H.A.; van Opzeeland, F.J.; Thalheim, D.; Werner, S.; de Jonge, M.I.; Hammerschmidt, S. Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection. Vaccines 2020, 8, 310.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop