Table 1.
Characteristics and results of included non-clinical studies.
| Study (year), country | Virus type a | Cell line | Inoculum b | Incubation (hours) | Control | Variants | Main findings |
|---|---|---|---|---|---|---|---|
| Ai, et al. (2022), China (19) | PV (VSV) | Vero | NA | 24 | B | BA.1, BA.1.1, BA.2, BA.3 | Bebtelovimab maintained its neutralization potency against all Omicron sublineages tested. |
| Andreano, et al. (2022), Italy (20) | Infectious | Vero | NR | 72 – 96 | B | BA.1, BA.2, BA.4, BA.5 | Bebtelovimab had high neutralization potency against all Omicron sublineages, showing an IC100 of 11.1, 15.6, 44.2, and 62.5 ng/ml against Omicron BA.1, BA.2, BA.4, and BA.5 respectively. |
| Arora, et al. (2022), Germany (21) | PV (VSV) | Vero | NA | 16 – 18 | B.1 | BA.1, BA.2, BA.2.12.1, BA.4, BA.5 | Bebtelovimab neutralized all emerging Omicron subvariants tested with similarly high efficacy. |
| Bruel, et al. (2022), France (22) | Infectious | U2OS-ACE2 GFP1-10 or GFP11 | NA | 18 | B.1.617.2 | BA.2, BA.4, BA.5 | Bebtelovimab remained fully active against Omicron BA.2, BA.4, and BA.5. Bebtelovimab displayed similar levels of binding and activation of NK-mediated antibody-dependent cellular cytotoxicity against all strains. |
| Cao, et al. (2022), China (23–26) | PV (VSV) | Huh-7 | 103 | 24 | B.1 | BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.13, BA.2.74, BA.2.75, BA.2.75.2, BA.2.75.4, BA.2.76, BA.2.77, BA.2.79, BA.3, BA.2.38, BA.2.38.1, BA.4, BA.4.6, BA.5, BA.5.1.12, BA.5.2.7, BA.5.5.1, BA.5.6.2, BF.16, BL.1 | Bebtelovimab showed potent neutralizing activity against the majority of assayed Omicron subvariants, except BA.2.38.1, BA.5.2.7, and BA.5.6.2. |
| Chakraborty, et al. (2022), India (51) | NA | NA | NA | NA | B | BA.1, BA.2, BA.2.12.1, BA.3, BA.4, BA.5 | Immunoinformatics simulation depicted L452R/Q498R double mutations in Omicron subvariants caused an approximately 6% reduction in binding affinities of bebtelovimab. |
| Duerr, et al. (2022), USA (27) | PV (HIV) and Infectious | 293T-ACE2 Vero/TMPRSS2 |
0.2 MOI 100 – 180 PFU |
NA | B.1 | AY.45, BA.1, BA.2, AY.45-BA.1 | Neutralization assays using infectious and pseudotyped viruses depicted bebtelovimab retained activity against all variants tested. |
| Fan, et al. (2022), USA (28) | PV (HIV) | 293T-ACE2 | NA | 48 | B.1 | BA.1, BA.2 | Bebtelovimab retained at least partial efficacy against Omicron variants by targeting a Class 3 receptor-binding domain epitope adjacent to the BA.1 and BA.2 mutations. |
| Gruell, et al. (2022), Germany (29) | PV (HIV) | 293T-ACE2 | NA | 48 | B.1 | BA.2, BA.2.12.1, BA.2.75, BA.4, BA.5 | Bebtelovimab demonstrated high BA.2.75 neutralizing potency (IC50 = 7.0 ng/ml), although the activity was lower than that against the other variants. |
| Iketani, et al. (2022), USA (30) | PV (VSV) | Vero | NA | 12 | B.1 | BA.1, BA.1.1, BA.2 | Bebtelovimab adequately treated all assayed Omicron sublineages, with IC50 of approximately 5 ng/ml. |
| Jian, et al. (2022), China (31) | PV (VSV) | Huh-7 | NA | 24 | B.1 | BA.4, BA.4.6, BA.4.7, BA.5, BA.5.9 | Bebtelovimab remained potent against R346-mutated BA.4 and BA.5 subvariants. |
| Kumar, et al. (2022), India (32) | Infectious | Vero/TMPRSS2 | 1×102 PFU | 16 – 40 | WA1 isolate | B.1.1.7, B.1.351, P.1, B.1.617.2, BA.1, BA.2 | Bebtelovimab showed binding and neutralization potential to Omicron and its sublineages. |
| Li, et al. (2022), China (33) | Infectious | HEK293F | NA | 60 | B | BA.1, BA.2, BA.3, BA.4 | Bebtelovimab preserved neutralizing activity against all Omicron sublineages tested. None of the four Omicron mutations, namely N440K, G446S, Q498R, and N501Y was found to disrupt the interaction with bebtelovimab, thus indicating its broad neutralizing activity. |
| Lusvarghi, et al. (2022), USA (34) | PV (HIV) | 293T-ACE2-TMPRSS2 | 1×105− 5×105 RLU | 48 | B.1 | BA.1 | Bebtelovimab maintained potency against BA.1 (IC50 = 3.2 ng/ml) comparable to B.1 (IC50 = 1.3 ng/ml), whereas antibody cocktail containing bebtelovimab, bamlanivimab, and etesevimab merely retained partial potency (IC50 = 32.5 ng/ml). |
| Misasi, et al. (2022), USA (35) | PV (VSV) | 293T-ACE2-TMPRSS2 | NA | 72 | B.1 | B.1.351, B.1.617.2, BA.1, BA.2, BA.2.12.1, BA.4, BA.5 | Bebtelovimab remained active against all variants tested. However, it fully escaped antibody neutralization within two to three rounds of repeated infection in vitro. |
| Sheward, et al. (2022), Sweden (37) | PV (HIV) | 293T-ACE2 | 1×105 RLU | 48 | B.1 | BA.2, BA.2.75, BA.5 | Bebtelovimab could neutralize BA.2.75 (IC50 = 15 ng/ml), but the potency was reduced by 7-fold as compared to B.1 (IC50 = 2 ng/ml). |
| Sheward, et al. (2022), Sweden (36) | PV (HIV) | 293T-ACE2 | 1×105 RLU | 44 – 48 | B.1 | BA.2.10.4, BA.2.75.2, BA.4.6, BA.5 | Bebtelovimab potently neutralized all emerging Omicron sublineages tested. |
| Starr, et al. (2022), USA (52) | NA | NA | NA | NA | B | BA.1, BA.2 | Deep mutational scanning revealed a broadening of the sites of escape from bebtelovimab binding BA.1 and BA.2 compared to the ancestral strain ascribable to mutations at residues K444, V445, P499, and G446. |
| Syed, et al. (2022), USA (38) | Infectious | 293T-ACE2/ACE2-TMPRSS2 and Vero-E6 | 50 PFU | 72 | WA1 isolate | B.1.617.2, B.1.1.529 | Bebtelovimab had potent neutralization activity against all variants tested, with IC50 of less than 10 ng/ml. |
| Takashita, et al. (2022), Japan (39) | Infectious | Vero-hACE2- TMPRSS2 |
1×103 FFU | 18 | NC002 isolate | BA.1.1, BA.1, BA.2, BA.2.12.1, BA.4, BA.5 | Bebtelovimab efficiently neutralized BA.2.12.1, BA.4, and BA.5, with similar IC50 values as the ancestral strain. |
| Takashita, et al. (2022), Japan (40) | Infectious | Vero-hACE2- TMPRSS2 |
1×103 FFU | 18 | NC002 isolate | BA.2, BA.2.75, BA.5 | Bebtelovimab efficiently neutralized BA.2.75 (IC50 = 6.21 ng/ml), however, this value was 4.4-fold higher compared to the ancestral strain. |
| Turelli, et al. (2022), Switzerland (41) | PV (HIV) and Infectious | Vero-E6/Calu-3 | 3×103 PFU | 48 | B.1 | B.1.1.7, B.1.351, P.1, B.1.617.2, BA.1, BA.2, BA.4, BA.5 | Bebtelovimab displayed good action against BA.4 and BA.5, with IC50 values of 12 ng/ml and 15 ng/ml respectively. In the Delta variant, spike mutations K444T, V445G, and G446V conferred resistance to bebtelovimab. In the Omicron BA.4 variant, mutations in the spike protein, namely K444T, V445G, and P499H suppressed neutralization activity of bebtelovimab. |
| Wang, et al. (2022), USA (42) | PV (VSV) | Vero-E6 and HEK293T | NA | 24 | B | BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4, BA.5 | Bebtelovimab retained exquisite in vitro potency against BA.2.12.1, BA.4, and BA.5, with IC50 below 3 ng/ml. |
| Wang, et al. (2022), USA (43) | PV (VSV) | Vero-E6 and HEK293T | NA | 24 | B.1 | BA.2, BA.2.12.1, BA.2.75, BA.4, BA.5 | Bebtelovimab retained potent neutralizing activity against all Omicron subvariants, with IC50 below 10 ng/ml. BA.2.75 demonstrated slight resistance to bebtelovimab, albeit modestly at a 3.7-fold loss in neutralization. |
| Wang, et al. (2022), USA (44) | PV (VSV) | Vero-E6 and HEK293T | NA | 24 | B.1 | BA.2, BA.4, BA.4.6, BA.4.7, BA.5, BA.5.9, BA.4/5-R346T, BA.4/5-R346S, BA.4/5-N658S | Bebtelovimab retained potent activity against all circulating forms of Omicron subvariants. |
| Westendorf, et al. (2022), USA (45) | PV (VSV) and Infectious | 293T-ACE2/ACE2-TMPRSS2 and Vero-E6 | NA | 72 | B.1 | B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.526, B.1.427/B.1.429, BA.1, BA.2 |
Bebtelovimab bound and potently neutralized all variants tested. |
| Yamasoba, et al. (2022), Japan (46) | PV (HIV) | HOS-ACE2-TMPRSS2 | 2 × 104 RLU | 48 | B.1.1 | BA.1, BA.2, B.1.617.2, BA.2.11, BA.2.12.1, BA.4, BA.5 | Bebtelovimab was approximately 2 times more effective against BA.2 and all Omicron subvariants tested as compared to wild-type virus. |
| Yamasoba, et al. (2022), Japan (47) | PV (HIV) | HOS-ACE2-TMPRSS2 | 2.5 × 104 RLU | 48 | B.1.1 | BA.2, BA.2.75, BA.4, BA.5 | Bebtelovimab demonstrated strong antiviral effect against BA.2, BA.4, and BA.5. In comparison, BA.2.75 showed about a 20 to 25-fold resistance to neutralization, suggesting that bebtelovimab may not be a good choice to treat BA.2.75 infection. |
| Zhang, et al. (2022), China (48) | Infectious | Vero | 600 PFU/ml | 96 | WIV04 isolate | B.1.617.2, BA.1 | Bebtelovimab exhibited neutralizing potency against wild-type (IC50 = 40.9 ng/ml), B.1.617.2 (IC50 = 50.8 ng/ml), and BA.1 (IC50 = 17.3 ng/ml). |
| Zhou, et al. (2022), USA (49) | PV (HIV) | 293T-ACE2-TMPRSS2 | NA | 72 | B.1 | B.1.1.7, B.1.351, P.1, B.1.617.2, BA.1 | Bebtelovimab retained binding and potent neutralization of all variants assessed, including BA.1 and BA.2 sublineages (IC50 = 5.1 and 0.6 ng/ml respectively). |
| Zhou, et al. (2022), USA (50) | PV (HIV) | 293T-ACE2 | 0.2 MOI | 48 | B.1 | B.1.617.2, BA.1, BA.2 | Bebtelovimab potently neutralized all variants tested, including BA.1 (IC50 = 26.2 ng/ml), BA.2 (IC50 = 11.5 ng/ml), and individual point mutated BA.2 viruses (IC50 range = 2.8 – 11.7 ng/ml). |
a
PV, pseudotyped virus; HIV, human immunodeficiency virus; VSV, vesicular stomatitis virus; MLV, murine leukemia virus.
b
The preclinical studies reported inoculum as 50% tissue culture infectious doses (TCID50), relative light units (RLU), plaque forming units (PFU), focus forming units (FFU), or transducing units (TU). The clinical study reported inoculum as multiplicity of infection (MOI).