Scientists in China have isolated a pair of neutralizing antibodies to SARS-CoV-2, the virus that causes COVID-19. The antibodies bind to the glycoprotein spike of the virus and prevent it from binding to the ACE2 receptor that allows the virus to enter host cells.
The scientists report that each antibody can bind to the receptor binding domain (RBD) of the spike glycoprotein and prevent entry into cells, but each binds to a different epitope on the glycoprotein spike.
The pair of antibodies – named B38 and H4 – were isolated from a blood sample taken from a patient who had contracted and recovered from SARS-CoV-2. In a study in a mouse model, the researchers showed the antibodies can reduce virus titers in infected lungs and suggest the antibodies could have valuable therapeutic benefits.
The researchers analyzed the RBD-B38 complex and generated images that show that the B38 antibody binds to amino acids in the RBD that bind to ACE2, thus preventing the virus from entering into host cells. The researchers used bio-layer interferometry to perform an epitope competition assay to determine whether the antibodies bound to the same epitope. “The Ni-NTA sensor labeled with the RBD was saturated with B38 IgG and H4 IgG was flowed through, or the sensor was first saturated with H4 IgG and B38 IgG was flowed through. Although RBD was saturated with the first antibody, the second antibody could still bind to RBD, but with some inhibition. This suggests that B38 and H4 recognize different epitopes on RBD with partial overlap,” explained the researchers.
In vitro experiments suggest that while the antibodies work on their own, they appear to have a much stronger neutralizing effect in tandem. The identification of two antibodies that bind to the RBD of SARS-CoV-2 should help to prevent immune escape by the virus. If viral epitopes mutate in a way that prevents one antibody from binding to the RBD, the other antibody may still be effective at neutralizing the virus.
The scientists suggest that providing a cocktail of both antibodies to patients diagnosed with COVID-19 could help to speed recovery. They also suggest that the antibodies could be provided to patients that have not contracted the disease and provide prophylactic benefits.
You can read more about the study in the paper – A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 – which was recently published in the journal Science. DOI: 10.1126/science.abc2241