Division of BioTherapeutics
Immune Activation and Tolerance
The Immune Activation and Tolerance group is headed by Dr. Bram Slütter. Vaccination is an experimental, but promising, treatment strategy for atherosclerosis. Previous work has shown that immunization of mice with modified LDL particles can reduce atherosclerotic lesion development, however such vaccines are difficult to produces and to characterize. Moreover, as the mechanism of action of this vaccine is unknown it is difficult to establish any correlates of protection and optimize the formulation to move these vaccines into clinical trials.
Our group works to:
1) understand the role of T-cells in the pathogenesis of atherosclerosis, with the aim of identifying athero-protective subsets that may be induced by immunization. For instance, we have recently described a protective role for CD8+ T-cells in advantage atherosclerotic lesion and are currently developing vaccine formulations to induce these cells.
Rather than using LDL particles as an immunogen we:
2) identify proteins/peptide from LDL that are presented in the atherosclerotic lesion, to serve as antigen for future vaccines.
3) develop nanoparticulate carrier systems that not only enhance the immunogenicity of the antigen, but also generate the desired type of T-cell response (e.g. Treg, CTL).
- Benne N., Duijn J. van, Kuiper J., Jiskoot W. & Slütter B. (2016), Orchestrating immune responses: How size, shape and rigidity affect the immunogenicity of particulate vaccines., Journal of Controlled Release 234: 124-134.
- Benne N., Jiskoot W., Kuiper J. & Slutter B.A. (2016), Stimulating antigen-specific regulatory T cells for an atherosclerosis vaccine, Journal of Immunology 196(1): 70.18.
- Duijn J. van, Jiskoot W., Kuiper J. & Slutter B.A. (2016), A tissue-specific phenotype for CD8+T cells in atherosclerotic lesions: role of the arterial microenvironment, Journal of Immunology 196(1): 186.10.
- Slütter B., van Braeckel-Budimir N., Abboud G., Varga S.M., Salek-Ardakani S., Harty J.T. (2017) , Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity. Science Immunology 2 (7)
- Slütter B., Pewe L.L., Lauer P., Harty J.T. (2013), Cutting edge: rapid boosting of cross-reactive memory CD8 T cells broadens the protective capacity of the Flumist vaccine. J Immunol.; 190(8): 3854-8.