March 29 - April 4 2021
A more effective bispecific antibody
Therapeutic antibodies seem to be an effective means of protection against and treatment of COVID-19. It is preferable to administer a combination of 2 antibodies targeting different regions of the virus, in order to enhance effectiveness and prevent viral variants that can evade treatment in the patient. However, formulating a “cocktail” of 2 antibodies is more complicated and more expensive, and makes greater demands on production facilities at a time when there is a heavy demand for vaccines and other treatment options. In response to these problems, Swiss and Czech researchers have recently developed a bispecific antibody, with the advantages of a combination of antibodies but within a single molecule.
Using computer simulations, they designed a bispecific antibody from 2 “parent” antibodies taken from patients who had recovered from SARS-CoV-2 infection. This bispecific antibody targets 2 distinct regions of the RBD (“Receptor Binding Domain”) of the surface spike viral protein, the domain which enables binding with the ACE2 cellular receptor. This synthetic antibody prevents entry of the viral particle into the cell. Its effectiveness was tested in vitro: it seems to be more effective than a mix of the 2 parent-antibodies in fixing itself to the S protein and in neutralizing the virus.
The scientists then validated the ability of this bispecific antibody to protect against COVID-19 using laboratory mice in which human ACE2 was expressed by cells from the upper and lower respiratory passages. They also showed that this antibody could be effective against the new UK, South African and Brazilian variants.
The researchers have thus developed a bispecific antibody having a synergistic neutralizing effect in relation to a mixture of the two parent antibodies. But before it can be added to the anti-COVID-19 arsenal, this antibody will have to be improved through genetic engineering by, for example, modifying it to prevent a mechanism that has already been described: facilitating infection by antibodies.