1.1 Therapeutic antibodies

In ‘passive immunisation’ a person is given antibodies that have been made in another person, an animal or in a laboratory. The technology for making antibodies in the laboratory was well established before the COVID-19 pandemic started. Consequently, at the start of the pandemic, when there was uncertainty about whether an effective vaccine could be produced in time, pharmaceutical companies put considerable effort into the production of human therapeutic antibodies against the SARS-CoV2 spike protein (Table 1).

The antibodies produced were ‘monoclonal’, meaning that they came from a single clone of B cells, and unlike naturally-produced polyclonal antibodies, monoclonal antibodies bind to just one position on an antigen. In producing therapeutic antibodies, the aim was to have an antibody that bound the receptor-binding domain (RBD) on the spike protein which could prevent the virus binding to its target, the ACE2 receptor.

These antibodies were initially given emergency authorisation, for use in preventing COVID-19 infection in vulnerable individuals and/or for treatment of hospitalised patients with serious disease. As the pandemic progressed it became clear that new variants of SARS-CoV2 sometimes evaded the protection produced by these antibodies. To reduce the risk of a virus variant evading immunity, formulations with two monoclonal antibodies (eg Casirivimab/ Imdevimab) were developed. Also, authorisation for use of these treatments was sometimes revoked or amended, if they became less effective.

It must be emphasised that these therapeutic antibody treatments are no substitute for active immunisation. A single treatment with a therapeutic antibody can cost £1000 - £1500, which contrasts with the typical cost of a vaccine, £1.50 - £15. Also, for immunological reasons, infusion of therapeutic antibodies may inhibit endogenous antibody production. Hence the reasons that therapeutic antibodies are licensed only for vulnerable or seriously-ill patients.

For the remainder of this week, we will look at active immunisation with vaccines containing virus or viral components.