About Us

The interdisciplinary HIVacToGC project aims at new approaches for therapy and prevention of HIV. Led by Prof. Dr. Ralf Wagner of the University of Regensburg, the team develops methods for the targeted transport of HIV antigens to lymph nodes.

The Federal Ministry of Education and Research (BMBF) supports the project in the context of the programme „targeted component delivery“ with a total funding of 2.4 million EUR over three years.

The Team of Prof. Wagner, Molecular Microbiology (Virology), Institute of Medical Microbiology and Hygiene, works together with the Institute of Pharmacy of the University of Regensburg (Prof. Dr. Breunig, Prof. Dr. Göpferich), the Institute of Biomolecular Nanotechnology of the TU Munich (Prof. Dr. Dietz), the Helmholtz Center Munich (Prof. Dr. Ertürk), as well as the companies 2bind GmbH and tilibit GmbH.

Our Mission

… is to rationally design a pharmaceutical HIV vaccine formulation supporting the controlled release of properly sized, biodegradable and adjuvanted DNA origami nanoparticles (DONPs) presenting an array of optimally spaced Env-trimers that are specifically targeted to secondary lymphoid organs, particularly lymph nodes (LN). Env trimers are engineered to adopt the closed pre-fusion conformation and optimally display epitopes for broadly neutralizing antibodies.

Our workgroup leaders

Prof. Dr. Wagner

Prof. Dr. Göpferich

Prof. Dr. Breunig

Prof. Dr. Dietz

Prof. Dr. Ali Ertürk

Dr. Jean-Philippe Sobczak

Dr. Thomas Schubert

Our Objectives

1) Development of a toolbox of DONPs decorated with state-of-the-art HIV vaccine candidates (Env) and targeting signals for specific delivery to lymph nodes and other secondary lymphoid tissues

2) Development of a hydrogel matrix for controlled release and targeted delivery of decorated DONP vaccine candidates to support GC formation and B cell maturation

3) Ex vivo characterization of decorated DONP-vaccines for structural and functional preservation of conjugated ligands (Env antigen, LN targeting, adjuvant)

4) To determine the specific in vivo targeting of DONP-vaccines to secondary lymphoid tissues and into lymph nodes. Provide in vivo safety and toxicity data for DONP-vaccines.

5) To assess and quantify germinal center formation, Tfh proliferation and B cell maturation in LNs and secondary lymphoid tissues, as well as the magnitude and quality of antibody responses induced in mice.

6) Ensure manufacturability (scale-up) and preparedness towards clinical development (SOPs, documentation etc.)

7) To ensure proper project management (coordination of tasks, internal communication and dissemination of results, data and IP management, promotion of PhDs and students)

Prof. Dr. Wagner

The group of Prof. Wagner has a strong track-record in the design, generation, pre-clinical and clinical validation of vaccine candidates, in particular for HIV. His team pioneered the utilization of recombinant VLPs and the use of RNA- and codon-optimization in biotechnology. This led to the foundation of GeneArt (now part of ThermoFisher Inc.), where Prof. Wagner served as CEO/CSO from 2000-2012. He is board member of several biotech companies and serving on the financing committee of Bayernkapital GmbH, a governmental VC vehicle. UR-MV will produce and conjugate the cargo to the DONPs, analyze the functionalized particles ex vivo (biophysical properties, antigenicity) and in vivo (biodistribution, immunogenicity), and coordinate the project.

Prof. Dr. Göpferich

The Department of Pharmaceutical Technology has an excellent competence for the targeted delivery of macromolecular drugs by using nanoparticles (Prof. Dr. Breunig) and hydrogels (Prof. Dr. Göpferich). The lab is fully equipped for polymer and hydrogel synthesis and characterization, as well as studies of nanoparticle release, characterization, functionality and toxicity testing in vitro. Within the proposed project, UR-PT will test established and develop novel hydrogel matrices for DONP vaccine delivery and assess the impact of the hydrogel matrix on the structural and functional characteristics in vitro and in vivo. Furthermore UR-PT leads safety/toxicity assessments and supports analysis of pharmacokinetics.

Prof. Dr. Breunig

The Department of Pharmaceutical Technology has an excellent competence for the targeted delivery of macromolecular drugs by using nanoparticles (Prof. Dr. Breunig) and hydrogels (Prof. Dr. Göpferich). The lab is fully equipped for polymer and hydrogel synthesis and characterization, as well as studies of nanoparticle release, characterization, functionality and toxicity testing in vitro. Within the proposed project, UR-PT will test established and develop novel hydrogel matrices for DONP vaccine delivery and assess the impact of the hydrogel matrix on the structural and functional characteristics in vitro and in vivo. Furthermore UR-PT leads safety/toxicity assessments and supports analysis of pharmacokinetics.

Prof. Dr. Dietz

Prof. Dr. Dietz has pioneered many aspects of DNA origami technology and successfully developed distinct nanoparticles of varying geometry and functionality. A patented, proprietary procedure for cost-efficient mass production is available that would enable generation of a product for first-in-human clinical trials. TUM-BN will contribute state-of-the-art expertise in programmable self-assembly of DONPs, including site-directed functionalization, biophysical characterization, and structural validation of functionalized DONPs and antibodies with high-end cryo electron microscopy.

Prof. Dr. Ali Ertürk

Prof. Dr. Ali Ertürk develops imaging and data analysis technologies enabling analysis of entire mouse bodies in an unbiased way on single cell level. These methods are already widely accepted and now being used to screen cancer metastasis, inflammation, etc. ITERM will contribute to the proposed project by applying the technology to track DONP-conjugates in whole mouse bodies. In addition, fluorescently labeled B cells, vasculature, and entire lymphatics can be tracked supporting detailed information regarding targeting of the vaccines on single cell level.

Dr. Jean-Philippe Sobczak

Tilibit GmbH, a spin-off founded in 2012 by Prof. Dr. Dietz (TUM-BN), is specialized in the development and production of functional DNA nanostructures, with the aim to translate the DNA origami technology into commercial applications, and currently the only company providing related services for therapeutic applications. Within the proposed project, Tilibit will develop protocols for DONP-manufacturing and support the compilation of SOPs and consideration of regulatory aspects.

Dr. Thomas Schubert

2bind GmbH is a leading service provider for biophysics focused on drug discovery and protein analytics. It has a track record of >600 projects with >100 customers. The company’s laboratory is fully equipped for biophysical characterization of molecular interactions and optimization of protein stability (nanoDSF, MST, ITC BLI, DLS etc.). 2bind will contribute by studying molecular interactions in relevant environments (e.g. serum, hydrogel) with regards to affinity, avidity, kinetics, thermodynamics and stoichiometry, as well as defining optimal buffer conditions for DONP-storage.