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. 2024 Feb 25;16(3):354.
doi: 10.3390/v16030354.

Tixagevimab/Cilgavimab: Still a Valid Prophylaxis against COVID-19 New Variants?

Affiliations

Tixagevimab/Cilgavimab: Still a Valid Prophylaxis against COVID-19 New Variants?

Anna Gidari et al. Viruses. .

Abstract

Background: this study aims to evaluate the efficacy of tixagevimab/cilgavimab (Evusheld™) against various SARS-CoV-2 variants, including newer Omicron sublineages, in an immunocompromised cohort and in vitro.

Study design: Conducted in Italy, this research involves immunocompromised patients who received Evusheld. It evaluates serum neutralization activity against different SARS-CoV-2 strains (20A.EU1, BA.5, BQ.1, XBB.1.5, XBB.1.16, and EG.5) before (T0), after 14 (T1), and after 30 (T2) days from the tixagevimab/cilgavimab injection. Furthermore, the in vitro activity of Evusheld against SARS-CoV-2 VOCs was evaluated.

Results: The cohort was composed of 72 immunocompromised patients. The serum neutralizing activity of tixagevimab/cilgavimab-treated patients was notably lower against newer variants such as BQ.1, XBB.1.5, XBB.1.16, and EG.5. Then, the in vitro study detailed specific EC50 values to quantify the activity of tixagevimab/cilgavimab against various SARS-CoV-2 VOCs. Newer variants like BQ.1 and XBB.1.5 exhibited notably lower neutralization, underscoring the challenges in effectively countering the evolving virus. Interestingly, tixagevimab/cilgavimab maintained reduced but still valid activity against EG.5 with an EC50 of 189 ng/mL and Cmax/EC90 of 110.7.

Conclusions: Tixagevimab/cilgavimab efficacy wanes against novel subvariants. This underscores the critical need for ongoing adaptation and vigilance in prophylactic strategies to effectively counter the dynamic and unpredictable nature of the COVID-19 pandemic.

Keywords: COVID-19; Omicron; SARS-CoV-2; cilgavimab; immunocompromised; tixagevimab; variant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Serum neutralization activity after tixagevimab/cilgavimab injection: neutralizing antibodies (NT90-Abs) titer decay curve for different SARS-CoV-2 variants. Time points: before the injection (T0), after 14 days (T1), and after 30 days (T2).
Figure 2
Figure 2
Dose-response inhibition test of tixagevimab/cilgavimab (1.2-1250 ng/mL) against 20A.EU1 (A), EG.5 (B), XBB.1.5 (C), and XBB.1.16 (D) strains of SARS-CoV-2 in Vero E6 cells (MOI 0.002). After 48 h of incubation on 96-well plates, supernatant titers were determined with plaque assay. Effective concentrations (EC50 and EC90) were calculated with four-parameter variable slope regression modeling. The data are presented as % of inhibition.

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