Hyeseon Cho and colleagues have developed bispecific antibodies – antibodies that can simultaneously bind to two different antigens – that target multiple regions of the SARS-CoV-2 spike protein and neutralize virus variants of concern. For the moment, COVID-19 antibody treatments work by sending in a cocktail of individual monoclonal antibodies to target various parts of the virus. But Cho et al. show that combining some of these monoclonal antibodies into a new bispecific antibody can create stronger antibodies that are more potent than the monoclonal cocktails – one bispecific antibody they tested, in particular, was 100 times more potent against the virus than a cocktail of its monoclonal parents. Two of the bispecific antibodies neutralized the original virus as well as the Alpha, Beta, Gamma, and Delta variants. In hamsters infected with SARS-CoV-2, two of the bispecific antibodies protected the animals from clinical disease. The researchers developed the bispecific antibodies from a pool of 216 monoclonal antibodies that target SARS-CoV-2 from convalescent COVID-19 patients, screening them for potency against the virus. The bispecific antibodies may be especially effective against the variants because they bind to non-overlapping areas of the viral spike and have limited contact with areas on the spike where variant mutations have occurred. “In the face of rapidly emerging SARS-CoV-2 variants that challenge our efforts to end the pandemic, our findings support the further exploration of bispecific antibodies that strategically combine antibody pairs as new tools to treat COVID-19,” Cho et al. write.
- Science Translational Medicine