Translating potent SARS-Cov2 neutralising nanobodies from the lab to the clinic

There is currently no cure or vaccine for Covid-19, passive immunotherapy however may prevent halt or ameliorate disease. We have identified multiple single domain antibodies (nanobodies) that neutralise live SARS-CoV-2 virus with picomolar efficacy in vitro. Working with Public Health England, we will test the efficacy of these neutralising nanobodies in a hamster model of mild to moderate disease with the prospect a novel nanobody-based medicine being developed for the treatment for Covid19. Nanobodies are so called because they are single domain (in fact heavy chain) containing the variable region and they derive from camelids. A nanobody is around 120 residues in length (~ 15 kD) and can access epitopes not normally seen by the human immune system. The variable gene sequences of camelids are similar to human and it has been proposed that nanobodies are less likely to be immunogenic than antibodies of other species. The relatively small size and stability of nanobodies gives them a unique advantage over human antibodies, which must be injected or given IV, nanobodies can be given as direct aerosolised delivery to the patient. Such an easy to administer and cheap therapy would transform the outlook for covid19. By the end of the project we aim to have established whether a neutralising nanobody to SARSCov2 is effective in an animal model of Covid19 and in particular whether a therapeutic / prophylactic dose can be delivered by nasal administration. In parallel the potential of candidate nanobodies to elicit virus escape mutants will be assessed.