Abstract
The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires effective therapies against coronavirus disease 2019 (COVID-19), and neutralizing antibodies are a promising therapy. A noncompeting pair of human neutralizing antibodies (B38 and H4) blocking SARS-CoV-2 binding to its receptor, ACE2, have been described previously. Here, we develop bsAb15, a bispecific monoclonal antibody (bsAb) based on B38 and H4. bsAb15 has greater neutralizing efficiency than these parental antibodies, results in less selective pressure and retains neutralizing ability to most SARS-CoV-2 variants of concern (with more potent neutralizing activity against the Delta variant). We also selected for escape mutants of the two parental mAbs, a mAb cocktail and bsAb15, demonstrating that bsAb15 can efficiently neutralize all single-mAb escape mutants. Furthermore, prophylactic and therapeutic application of bsAb15 reduced the viral titer in infected nonhuman primates and human ACE2 transgenic mice. Therefore, this bsAb is a feasible and effective strategy to treat and prevent severe COVID-19.
【초록키워드】 COVID-19, coronavirus disease, neutralizing antibody, antibodies, SARS-CoV-2, ACE2, coronavirus, pandemic, therapy, severe COVID-19, monoclonal antibody, SARS-CoV-2 variant, Prophylactic, delta variant, human ACE2, Neutralizing activity, escape mutant, therapeutic, Neutralizing, receptor, mAbs, binding, mAb, escape mutants, Efficiency, acute respiratory syndrome, transgenic mice, effective therapy, treat, selective, viral titer, Prevent, effective, neutralize, greater, selected, described, develop, reduced, less, feasible, parental, 【제목키워드】 SARS-CoV-2, Human monoclonal antibody,