Fig. 1. Combination of HLX70 and HLX71 increased efficacy in SARS-CoV-2 neutralization.

a Schematic diagram for treatment schedule of HLX71 in the hACE2-transgenic mouse model. A single dose of HLX71 (15 or 50 mg/kg) or PBS control was injected intraperitoneally 2 h after the SARS-CoV-2 challenge. The mortality of the mice was recorded every day for 5 days. b Survival curve of SARS-CoV-2-infected mice treated with HLX71. *P < 0.05. c Affinity analysis of the binding of HLX70 (left) and HLX71 (right) to SARS-CoV-2 RBD. d RBD-blocking activity of HLX71 is enhanced by HLX70. HLX70 (0.05 μg/mL) was mixed with serially diluted HLX71 and incubated with RBD-His. The mix was then added to the 293T-hACE2 cell suspension, and an anti-His-PE antibody was used for detection. CI (combination index) values were calculated by CompuSyn software. e RBD-blocking activity of HLX70 is enhanced by HLX71. HLX71 (0.5 μg/mL) was mixed with serially diluted HLX70 and incubated with RBD-His. The blocking rate was measured the same way as d. f HLX70 was mixed with HLX71 at the ratio of 1:2, 1:3, 1:5, 1:10, and 1:30. Threefold serial dilutions of the mixes were added to ~500 PFU of SARS-CoV-2 virus solution, and the neutralization potency was assessed in Vero cells using PRNT. The x axis shows the concentrations of the HLX70. g In vivo efficacy of HLX70 + HLX71 combination. BALB/c mice were treated with HLX70 (n = 5), HLX71 (n = 5), or HLX70 + HLX71 combination (n = 5) 2 h after infection of 1.6 × 10⁴ PFU of MASCp6. Five days after the virus challenge, mice were sacrificed to analyze the virus burden in the lung and trachea. Virus titer was demonstrated as RNA copies per gram tissue. ns, not significant; *P < 0.05. h HLX71 neutralization activity against HLX70-resistant SARS-CoV-2 pseudovirus mutants. i Neutralization activity of HLX70 and HLX71 against pseudoviruses with multiple mutations.