Measurement of the GFP signal from ACE2-producing Expi293F cells incubated with GFP-positive SARS-CoV-2 VLPs

Virus-like-particle based technologies

Virus-like-particles (VLP) are empty viral envelopes not containing viral genetic material and are therefore not infectious. They can be produced by the co-expression of the structural proteins of the respective virus in suitable expression systems such as insect cells. We will apply these recombinant VLPs as vaccines and diagnostic tools. In addition, we will generate modified VLPs to facilitate research of infection mechanisms and drug development. Furthermore, we will investigate innovative VLP technologies for the targeted transport of drugs into cells.

Dr Maren Schubert

Head

Dr Maren Schubert
Research Group Leader

Our research

illustration
A) GFP-positive SARS-CoV-2 VLPs (green) bind to ACE2-producing Expi293F cells. B) Measurement of the GFP signal from ACE2-producing Expi293F cells incubated with GFP-positive SARS-CoV-2 VLPs after addition of antibodies or inhibitors. A non-binding antibody (red) has no effect on the GFP signal, as it does not prevent the VLPs from binding to the cells. In contrast, the measured GFP median decreases in a concentration-dependent manner after the addition of soluble ACE2 (yellow) or a neutralizing antibody (STE90-C11, green).

Our technology-oriented research is based on the use of recombinant virus-like particles (VLPs), which can be produced by co-expressing the structural proteins of the respective virus. These VLPs can mimic the shells of real viruses very authentically, but are not infectious themselves, which enables research and use outside of laboratories with higher safety levels.

Such authentic VLPs can be used directly as vaccines, one example being the already approved Cervix vaccine against human papillomaviruses. We will research and develop further VLPs as potential vaccine candidates against infectious diseases. At the same time, authentic VLPs serve as a diagnostic tool to evaluate the immune response, e.g., in reaction to a vaccination or the spread of infectious diseases, which is particularly relevant in the context of climate change in terms of the One Health approach.

In addition, modified VLPs are important tools for basic research. Modifications inside the VLP, such as the introduction of a fluorescent protein that does not alter the authentic VLP surface, enable investigations of infection mechanisms. These VLPs can also be used for drug development, as the inhibition of binding and fusion of modified VLPs and cells by a drug can be measured and quantified in high-throughput process (Figure 1). Drugs like neutralizing antibodies can thus be analyzed quickly, effectively, and in laboratories with a lower safety level, which is an important step in terms of pandemic resilience.

Schematic experiment overview.
Plasmid-based expression system in High Five insect cells. After adding the expression plasmids and polyethyleneimine, the VLPs can be harvested after approximately 96 hours.

In addition, we want to generate recombinant VLPs that, thanks to modifications, are able to deliver drugs into cells in a targeted and particularly efficient manner, what still poses a major challenge for various therapeutic approaches. Here, we also aim to develop solutions for latent viral infections.

To this end, we mainly use plasmid-based expression in insect cells (Figure 2), a highly efficient system for the production of VLPs (Lampinen et al. 2024). Compared to the baculoviral systems commonly used for insect cells, cell vitality remains high throughout the production process and no baculoviral particles and proteins are produced in parallel to the recombinant VLPs, which improves VLP quality. In addition, the system is very flexible and allows for easy adaptation of individual proteins and production rates by exchanging the respective plasmids.