Engineering Antigen Trafficking
We investigate how endogenous extracellular vesicles control adaptive immunity and how these natural trafficking pathways can be engineered to improve vaccines and immunotherapies.
We investigate how endogenous extracellular vesicles control adaptive immunity and how these natural trafficking pathways can be engineered to improve vaccines and immunotherapies.
© J. Greune
PD Dr. rer. nat. Jan Kranich
AG Brocker
Institute for Immunology
Biomedical Center
LMU Munich
Großhadernerstr. 9
DE- 82152 Planegg-Martinsried
+49 (0)89 2180 75660
jan.kranich@med.uni-muenchen.de
Engineering Antigen Trafficking
We investigate how endogenous extracellular vesicles control adaptive immunity and how these natural trafficking pathways can be engineered to improve vaccines and immunotherapies.
A major focus of our work is understanding how antigens are transported through lymphoid tissues and delivered to B-cell follicles during the initiation of immune responses. We discovered that endogenous EVs constitute a previously unrecognized pathway for antigen trafficking to follicular dendritic cells (FDCs), providing a physiological mechanism for antigen delivery that operates independently of immune complexes and complement.
Building on this discovery, we developed EV-targeted antigens (EVtAg) by genetically fusing vaccine antigens to phosphatidylserine-binding proteins. This approach redirects soluble antigens onto endogenous EVs, enabling rapid accumulation on FDCs, accelerated germinal center responses, increased antibody affinity maturation, and enhanced neutralizing antibody responses.
Our long-term goal is to establish engineering antigen trafficking as a new design principle for vaccines. Rather than solely optimizing antigen structure or vaccine formulation, we seek to control where antigens travel within the immune system by exploiting endogenous extracellular vesicles as physiological antigen carriers.
OrcID: https://orcid.org/0000-0002-9928-4132
Phosphatidylserine-positive extracellular vesicles boost effector CD8+ T cell responses during viral infection.
Rausch L, Flaskamp L, Ashokkumar A, Trefzer A, Ried C, Buchholz VR, Obst R, Straub T, Brocker T, Kranich J.
Proc Natl Acad Sci U S A. 2023 Apr 18;120(16):e2210047120. doi: 10.1073/pnas.2210047120. Epub 2023 Apr 11.
PMID: 37040405
Binding of phosphatidylserine-positive microparticles by PBMCs classifies disease severity in COVID-19 patients.
Rausch L, Lutz K, Schifferer M, Winheim E, Gruber R, Oesterhaus EF, Rinke L, Hellmuth JC, Scherer C, Muenchhoff M, Mandel C, Bergwelt-Baildon M, Simons M, Straub T, Krug AB, Kranich J, Brocker T.
J Extracell Vesicles. 2021 Dec;10(14):e12173. doi: 10.1002/jev2.12173.
PMID: 34854246
Predicting single-cell gene expression profiles of imaging flow cytometry data with machine learning.
Chlis NK, Rausch L, Brocker T, Kranich J, Theis FJ.
Nucleic Acids Res. 2020 Nov 18;48(20):11335-11346. doi: 10.1093/nar/gkaa926.
PMID: 33119742
In vivo identification of apoptotic and extracellular vesicle-bound live cells using image-based deep learning.
Kranich J, Chlis NK, Rausch L, Latha A, Schifferer M, Kurz T, Foltyn-Arfa Kia A, Simons M, Theis FJ, Brocker T.
J Extracell Vesicles. 2020 Jul 16;9(1):1792683. doi: 10.1080/20013078.2020.1792683.
PMID: 32944180