Translating potent SARS-Cov-2 neutralising nanobodies from the lab to the clinic

Lead Research Organisation: The Rosalind Franklin Institute
Department Name: Research

Abstract

There is currently no cure for Covid-19. However, treatment with antibodies that block SARS-CoV2 from infecting cells may halt or ameliorate disease. We have produced very potent mini-antibodies or nanobodies that neutralise the virus in "test-tube" experiments with 100 % efficiency. The small size and stability of the nanobodies make them candidates for direct delivery into the lungs using a nebuliser device with the idea of rapidly reducing infection in the airways. The highly neutralising SARS-Cov2 nanobodies that we have generated are ready for animal tests. Successful demonstration of activity in animals will be the key step to developing this novel way of treating Covid19 with antibodies.

Technical Summary

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 and the Department of Infection Biology, University of Liverpool, we will test the efficacy of these neutralising nanobodies in a hamster model of mild to moderate disease with the prospect of developing a novel nanobody-based medicine for the treatment for Covid19.
Nanobodies are single domain antibodies comprising the variable region of a subset of heavy chain only antibodies 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 SARS- Cov2 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.

Publications

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Description Evaluation of SARS-Cov-2 nanobodies in Syrian Hamster model of Covid 19 
Organisation University of Liverpool
Department Institute of Infection and Global Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in the the identification, production and and characterisation of nanobody reagents for testing in vivo
Collaborator Contribution Expertise in Syrian Hamster model of Covid19 analysis of data including virology and histopathology.
Impact The collaboration is multi-discilionary combining , biochemistry, structural biology, virology and pharmacology. A the predict only begin 1/12/20 there are no outcomes that can beformally reported yet.
Start Year 2020