Ultrapotent Bispecific Antibodies That Can Simultaneously Bind to Two Different Antigens Neutralize SARS-CoV-2 Variants

Researchers 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.

The team of researchers from the National Institute of Allergy and Infectious Diseases (NIAID; Bethesda, MD, USA) isolated monoclonal antibodies targeting the SARS-CoV-2 spike protein from donors who had recovered from COVID-19. Pairs of potent monoclonal antibodies that bound distinct regions of the spike protein were combined into bispecific antibodies. These bispecific antibodies prevented SARS-CoV-2 variants of concern from infecting cells in vitro and prevented disease in hamsters infected with SARS-CoV-2.


Currently, COVID-19 antibody treatments work by sending in a cocktail of individual monoclonal antibodies to target various parts of the virus. However, the NIAID researchers showed 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,” stated Hyeseon Cho from the team of NIAID researchers.

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