In vitro activity of therapeutic antibodies against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5

Abstract

The replacement of the Omicron BA.1 variant of SARS-CoV-2 by the BA.2 and the rapid growth of the BA.5 sub lineage, which have both different sets of mutations in the spike glycoprotein, alters the spectrum of activity of therapeutic antibodies currently licensed in the European Union. Using clinical strains of the Omicron BA.2 and BA.5 variants, we compared the neutralising power of monoclonal antibodies against the Omicron BA.1, BA.2 and BA.5 variants, using an ancestral strain (lineage B.1, D614G) and a Delta variant strain as reference. Sotrovimab/Vir-7831 is less active against BA.2 than against BA.1 (fold change reduction ~ 1,4) and even less active against BA.5 (fold change reduction ~ 2.7). Within the Evusheld /AZD7442 cocktail, Cilgavimab/AZD1061 is more active against BA.2 and BA.5 than against BA.1 (fold change increase ~ 32), whilst the very low activity of Tixagevimab/AZD8895 against BA.1 is not enhanced against BA.2 nor BA.5. In total, compared to BA.1, the activity of the Evusheld/AZD7442 is significantly improved against BA.2 while BA.5 is intermediate but closer to BA.2.

SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

“… 24 Using clinical isolates, we confirm findings from early seminal contributions. 25 , 26 , 27 , 28 , 29 , 30 Observations using pseudovirus have seen greater antibody evasion of BA.5 compared to its parent BA.2 following different vaccine schedules. Importantly herein, we observe the peak responses following three doses of BNT162b2 to generate antibody neutralising breadth to equally cover BA.2 and BA.5 and this is consistent with that recently observed by Bowen and colleagues.…”

“…In contrast, the class 3 antibody Sotrovimab targets a highly conserved region of the sarbecovirus RBD 32 and based on its neutralising epitope should retain activity against both BA.2 and BA.5. Many recent studies on Omicron lineages BA.1, BA.2 and BA.5 have studied the potency of clinical monoclonal antibodies in detail 26 , 27 , 28 , 33 , 34 and whilst each study has demonstrated potency reductions, they vary with respect to fold reductions per variant tested. In the context of the latter work, the fold reductions for Sotrovimab and Evusheld herein are within twice of that of the median of the above cited studies.…”

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

“…As other Omicron sublineages, BA.4 and BA.5 escape most neutralizing mAbs. 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 The neutralization profile of BA.4 and BA.5 is similar to that of BA.2, with only cilgavimab and bebtelovimab being efficient against these strains with high potency. 35 , 36 , 37 , 38 , 39 Animal models revealed that some mAbs do not only rely on neutralization for therapeutic efficacy.…”

The Epidemiological Features of the SARS-CoV-2 Omicron Subvariant BA.5 and Its Evasion of the Neutralizing Activity of Vaccination and Prior Infection

“…BA.5 shares common mutations in the spike with BA.2, except for del69-70, L452R, F486 V, and R493Q, a reversion mutation [ 36 ]. Structural analysis indicated that L452R/Q conferred resistance largely to class 2 and 3 RBD mAbs and affected the sensitivity to vaccine-induced neutralizing antibodies, especially L452R [ 37 ].…”

“…Moreover, the neutralization testing of live viruses showed that the monoclonal antibodies casirivimab and sotrovimab and casirivimab and imdevimab lost neutralizing activity against BA.5 [ 49 ]. Compared with BA.1, sotrovimab is less active against BA.5, with a 2.7-fold reduction [ 36 ]. BA.5 has been found to be 4–20-fold more resistant to cilgavimab and evusheld than BA.2 [ 15 , 50 ].…”