Are nanobodies more effective than antibodies?

Hopes have been raised for the treatment serious cases of COVID-19 by monoclonal antibodies. These drugs are now on the market, though certain obstacles have prevented their widespread use: their high cost, their short therapeutic window (they must be given between the 4^th and the 7^th day of the illness), the huge numbers of patients involved and the appearance of resistant variants. New treatment options are therefore necessary.

Ram Sasisekharan at the Massachusetts Institute of Technology, Cambridge, USA has promoted the development of nanobodies (tiny camelid-derived antibodies) as a treatment for COVID-19. His work is based on the study published earlier this year by Paul-Albert Koenig and his collaborators. These researchers immunised lamas and alpacas with the spike (S) protein of SARS-CoV-2 and were thus able to identify the nanobodies that specifically bind to the RBD (Receptor Binding Domain) of the S protein, the domain where binding with the ACE2 cellular receptor occurs (see news-COVID-19.info 8-14^th February 2021). The researchers then constructed biparatopic nanobodies, that is, with two antigen binding domains in a single molecule, by merging two nanobodies with two different epitopes (those parts of a molecule that recognize an antigen). These biparatopic nanobodies are much more effective than conventional nanobodies in neutralizing SARS-CoV-2 infection. Among the identified nanobodies, some do not target the amino acids 417, 484 and 501 (mutations found in Brazilian, South African or English variants) and may therefore remain effective against these variants. Finally, the nanobodies have certain advantages over traditional therapeutic antibodies: they are easy and inexpensive to produce, they are stable, and their miniscule size allows them to reach targets inaccessible to conventional antibodies.

Recently, experts from regulatory bodies, universities, and pharmaceutical and biotechnology companies have called for the development of small, easy-to-administer molecules against SARS-CoV-2. A biparatopic nanobody has already been approved by European and American health regulators for the treatment of some purpura and several are under investigation for the treatment of cancers or infectious diseases such as COVID-19.