Activity of human broadly neutralising antibodies in a SARS-CoV-2 primate model
Project leader: Prof. Dr. Thomas Schulz
Key area
- Antiviral strategies: agents and vaccines, antibodies
Who is involved?
- Prof. Dr. Thomas Schulz (Project leader, MHH)
- Prof. Dr. Thomas Krey (MHH)
- Prof. Dr. Stefan Pöhlmann (DPZ)
What is the aim?
This project aims to develop broadly neutralising human monoclonal antibodies against SARS-CoV-2 and its clinically important variants, as well as against related sarbecoviruses, which could serve as a potential starting point for new zoonotic outbreaks. The project builds on the successful cloning of broadly neutralising human antibodies against SARS-CoV-2 from B cells of COVID-19 patients. In order to extend the activity of these antibodies to related sarbecoviruses of animal origin, transgenic mice carrying a human immunoglobulin repertoire (Trianni mice) will be sequentially immunised with recombinant S-proteins of different sarbecoviruses in collaboration with scientists in Erlangen in order to induce the formation of broadly cross-reactive antibodies. Such antibody-producing B cells from these mice will then be selected using recombinant S proteins, their immunoglobulin genes analysed by single cell sequencing, and the monoclonal antibodies encoded by them produced recombinantly and tested for their ability to neutralise phylogenetically more distant sarbecoviruses. Monoclonal antibodies exhibiting the desired capabilities will then be tested in animal models, including a primate model, for their protective effect in an infected host. In the long term, such antibodies will be further developed as improved therapeutics and brought into the clinic.