Antibody cocktail effective against variants of SARS-CoV-2

Abstract

Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus with a high mutation rate. Importantly, several currently circulating SARS-CoV-2 variants are associated with loss of efficacy for both vaccines and neutralizing antibodies. Methods We analyzed the binding activity of six highly potent antibodies to the spike proteins of SARS-CoV-2 variants, assessed their neutralizing abilities with pseudovirus and authentic SARS-CoV-2 variants and evaluate efficacy of antibody cocktail in Delta SARS-CoV-2-infected hamster models as prophylactic and post-infection treatments. Results The tested RBD-chAbs, except RBD-chAb-25, maintained binding ability to spike proteins from SARS-CoV-2 variants. However, only RBD-chAb-45 and -51 retained neutralizing activities; RBD-chAb-1, -15, -25 and -28 exhibited diminished neutralization for all SARS-CoV-2 variants. Notably, several cocktails of our antibodies showed low IC50 values (3.35–27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including United Kingdom variant B.1.1.7 (Alpha), South Africa variant B.1.351 (Beta), Brazil variant P1 (Gamma), California variant B.1.429 (Epsilon), New York variant B.1.526 (Iota), and India variants, B.1.617.1 (Kappa) and B.1.617.2 (Delta). RBD-chAb-45, and -51 showed PRNT50 values 4.93–37.54 ng/ml when used as single treatments or in combination with RBD-chAb-15 or -28, according to plaque assays with authentic Alpha, Gamma and Delta SARS-CoV-2 variants. Furthermore, the antibody cocktail of RBD-chAb-15 and -45 exhibited potent prophylactic and therapeutic effects in Delta SARS-CoV-2 variant-infected hamsters. Conclusions The cocktail of RBD-chAbs exhibited potent neutralizing activities against SARS-CoV-2 variants. These antibody cocktails are highly promising candidate tools for controlling new SARS-CoV-2 variants, including Delta.

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

“…Importantly, the prophylactic effects of these Abs were demonstrated in an AAV-hACE2 mouse model and a hamster model, and the cocktail of RBD-chAb-25 and 45 showed highly promising therapeutic effects [ 50 ]. Notably, several antibody cocktails showed low IC 50 values (3.35–27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including Alpha, Beta, Gamma, Epsilon, Iota, Kappa and Delta variants [ 75 ]. Furthermore, the therapeutic treatment with an antibody cocktail of RBD-chAb-15 and 45 effectively protected hamsters from infection with the Delta SARS-CoV-2 variant [ 75 ].…”

“…Notably, several antibody cocktails showed low IC 50 values (3.35–27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including Alpha, Beta, Gamma, Epsilon, Iota, Kappa and Delta variants [ 75 ]. Furthermore, the therapeutic treatment with an antibody cocktail of RBD-chAb-15 and 45 effectively protected hamsters from infection with the Delta SARS-CoV-2 variant [ 75 ].…”

“…Zost et al further showed a synergistic effect of Abs in a mouse model with adenovirus-induced transient expression of human ACE2 in addition to their in vitro experiments [ 100 ]. In addition, Su et al, showed that the cocktail of RBD-chAb-25 and 45 not only exhibits synergistic neutralizing ability, but it is also likely to retain therapeutic potential for SARS-CoV-2 mutants [ 50 , 75 ]. In addition, some recent studies showed that the accumulation of somatic mutations increased the diversity and potency of neutralizing Abs against SARS-CoV-2 [ 219 – 222 ].…”

Neutralizing Monoclonal Antibodies Inhibit SARS-CoV-2 Infection through Blocking Membrane Fusion

“…A reduced neutralization activity of therapeutic mAbs or sera from convalescent patients against the SARS-CoV-2 variants carrying genetic mutations in the S proteins, such as SARS-CoV-2 Alpha and Beta variants, has been reported ( 32 ). However, a neutralizing chimeric antibody RBD-chAb-45 against the RBD of SARS-CoV-2 S protein exhibited strong neutralizing potency against SARS-CoV-2 D614G, Alpha, Beta, Gamma, Delta, Epsilon, Iota, and Kappa variants ( 33 ). Therefore, the ability of S2-4D, S2-5D, and S2-8D to neutralize SARS-CoV-2 Alpha, Gamma, Delta, and Epsilon variants was examined by plaque reduction assay.…”

Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice

“…We showed that cocktails of these antibodies can neutralize D614G, Epsilon (B.1.429) and Kappa (B.1.617.1) strains, as well as four VOCs (Alpha, Beta, Gamma and Delta). The prophylactic and therapeutic activities of the individual neutralizing antibodies or antibody cocktails were then confirmed in D614G- and Delta-variant-infected mouse and hamster models (Liang et al, 2021). Although antibody therapy was effective in neutralizing the relevant VOCs of the time, we later found that Omicron BA.1 appears to be refractory to neutralization by our six mAbs.…”