What is your role in the LWNVIVAT project?

Together with Michael Hust and Federico Bertoglio, I produce WNV antigens and virus-like particles (VLPs) and generate antibodies against WNV using phage display.

What is the primary goal of your research?

The goal of my research is to develop a flexible, insect cell-based expression platform for producing various VLPs for vaccination purposes, as well as for generating and validating neutralizing antibodies and other therapeutics. Additionally, I aim to functionalize VLPs for a broader range of applications.

What is a WNV-VLP?

A WNV-VLP is an empty virus shell composed of structural WNV surface proteins. These particles resemble the surface of the infectious WNV particle but are entirely safe, as they contain no viral genetic material and are therefore non-infectious.

What is the potential of WNV-VLPs? Will they be used as a vaccine or in combination with other strategies?

WNV-VLPs have the potential to be used as a standalone vaccine, but we aim to enhance their effectiveness by combining them with the generated antibodies to boost the immune response. Additionally, we will use WNV-VLPs to generate antibodies through phage display and to test these antibodies in cell-based assays for neutralization.

How do you produce these VLPs?

We express the VLPs in insect cells, which yield high production levels and support complex post-translational modifications. Unlike the commonly used Baculovirus Expression Vector System (BEVS) for insect cells, we use a plasmid-based transient expression system. This allows us to test multiple constructs in various ratios simultaneously within a short time frame (96 hours) to identify the optimal composition while achieving similar yields as with BEVS. Additionally, this approach avoids baculovirus or baculoviral protein contamination, which is often a challenge with BEVS, and it maintains high insect cell viability during production, ensuring a high quality of the produced proteins/VLPs.

What are the latest results you have achieved?

We have constructed multiple expression vectors, produced initial antigens, and tested the first WNV-VLP compositions of WNV strain 1. We also verified the successful expression of WNV-VLPs using ELISA, NTA, and TEM.

What are the next steps in your research?

We aim to develop an assay to measure the fusion of WNV-VLPs with cells, which will allow us to test our antibody candidates for neutralization. Additionally, we plan to obtain blood samples to begin generating immune antibody phage libraries.