QUAL: Design of long-acting SARS-COV-2 neutralizing antibodies

The elderly and people with weakened immune systems do not necessarily respond effectively to vaccines. There is therefore an urgent need for specific treatment that prevents the development of severe COVID-19. Development of monoclonal antibodies that specifically target the virus followed by blocking of infection and elimination from the body is an attractive strategy for both therapy and preventive treatment. This is supported by recent clinical data. However, antibody treatment is expensive and unfortunately not necessarily available to those in need on a global scale. As such, in collaboration with international non-profit organizations, we have isolated fully human monoclonal antibodies that effectively block all relevant SARS-CoV-2 strains of concern. The antibodies bind to independent and conserved binding sites on the spike protein, and can therefore be given as a cocktail. However, uptake and availability of such monoclonal antibodies has been extremely limited due to high doses required and intravenous formulations. In this project, we have tested a unique antibody technology, patented and developed by us, to investigate whether the technology can be used to extend the plasma half-life and improve the distribution of IgG1 monoclonal antibodies directed against SARS-CoV-2. The results show that the monoclonal antibodies combined with the technology can be produced as efficiently as the parental antibodies. Furthermore, we show that the technology provides significantly extended duration of action in a humanized mouse model under optimal conditions that are predictive of pharmacokinetics in a human setting. The very good data now motivates verification of the technology in non-human monkeys.